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Purpose: Sentinel lymph node biopsy (SLNB) has become a widely accepted staging procedure for both breast carcinoma and melanoma. The aim of our study was to systematically review different SLNB techniques and perform a meta-analysis for corresponding identification and false-negative rates. Methods: A systematic review of the literature on SLNB in patients with early stage breast carcinoma and melanoma was performed. Only original study groups were included. The SLN identification rate and false negative rate were pooled for patients with breast carcinoma or melanoma according to radiocolloid tracer, blue dye, indocyanine green (ICG), or a combination of a radiocolloid tracer with blue dye or ICG. Results: Between 1992 and 2012, a total of 154 studies (88 breast carcinoma and 66 melanoma) were reported that met our eligibility criteria. These studies included a total of 44,172 patients. The pooled SLN identification rate in breast carcinoma and melanoma patients using solely blue dye was 85% (range: 65-100%) and 84% (range: 59-100%), while for radiocolloid alone it was 94% (range: 67-100%) and 99% (range: 83-100%), respectively. Using a combination of radiocolloid and blue, identification rates were 95% (range 94-95%) and 98% (range: 98-98%). Conclusions: The current meta-analysis provides data that favors the use of radiocolloid or radiocolloid combined with a blue dye for SLN identification. Perfoiming SLNB with radiocolloid alone is the technique of choice for experienced surgeons, since blue dye has multiple disadvantages. SLNB using ICG as a fluorescent dye seems a promising technique for the near future. (C) 2016 Elsevier Ltd. All rights reserved.

Breast-conserving therapy has become a preferred option in the treatment of early breast cancer. Current breast-conserving therapy includes 3–5 weeks of external beam radiotherapy to the whole breast, sometimes followed by a 1–2-week boost to the tumor bed. However, the duration of the radiation regimen can be prohibitive for the elderly, infirm or immobile patients, those patients who live far from the cancer center, or those who have difficulty taking an extended leave of absence. We propose to treat these patients with a single dose of radiation preoperatively, thereby shortening the total treatment time. This is a single-arm phase II case series trial, conducted on 120 patients with early breast cancer who will be accrued from multidisciplinary breast cancer clinics. These patients will have research biopsies taken at the time of enrollment and will undergo radiation planning with CT simulation and PET/MRI. A single dose of 21 Gy will then be delivered in the prone position to the tumor. A second research biopsy will be taken, then lumpectomy will be performed. This entire procedure will be completed within 1 week (7 days). The primary endpoint is rate of toxicity (≥grade 2 fibrosis), and secondary endpoints include cosmetic results, quality of life, and rate of recurrence. This study will assess the toxicity associated with using a single preoperative dose of radiation as a replacement for standard adjuvant radiotherapy in breast-conserving therapy. Results of this trial will guide the design of a possible phase III study. Trial registration: Clinicaltrials.gov identifier: NCT02212860

Surgery for early stage breast carcinoma is either total mastectomy (complete breast removal) or surgical lumpectomy (only tumor removal). The lumpectomy or partial mastectomy is intended to preserve a breast that satisfies the woman's cosmetic, emotional and physical needs. But in a fairly large number of cases the cosmetic outcome is not satisfactory. Today, predicting that surgery outcome is essentially based on heuristic. Modeling such a complex process must encompass multiple scales, in space from cells to tissue, as well as in time, from minutes for the tissue mechanics to months for healing. The goal of this paper is to present a first step in multiscale modeling of the long time scale prediction of breast shape after tumor resection. This task requires coupling very different mechanical and biological models with very different computing needs. We provide a simple illustration of the application of heterogeneous distributed computing and modular software design to speed up the model development. Our computational framework serves currently to test hypothesis on breast tissue healing in a pilot study with women who have been elected to undergo BCT and are being treated at the Methodist Hospital in Houston, TX.

Despite the successful application of sentinel node mapping in breast cancer patients, its use in patients with a history of previous excisional biopsy of the breast tumors is a matter of controversy. In the present study we evaluated the accuracy of sentinel node biopsy in this group of patients and compared the results with those in whom the diagnosis of breast cancer was established by core needle biopsy. Eighty patients with early stage breast carcinoma were included into our study. Forty patients had a history of previous excisional biopsy and the remainder 40 had undergone core needle biopsy. Intradermal injections of 99mTc-antimony sulfide colloid as well as patent blue were both used for sentinel node mapping. Sentinel nodes were harvested during surgery with the aid of surgical gamma probe. All patients underwent standard axillary lymph node dissection subsequently. Detection rate was 97.5 per cent for both groups of the study. Number of detected sentinel node during surgery was not significantly different between groups. False negative rate was 0 per cent for both groups of the study. In conclusion sentinel node biopsy is reliable in patients with previous history of excisional biopsy of the breast tumors and has a low false negative rate.

NSABP Protocol B-09 reported primary breast carcinomas expressing estrogen (ER) and progestin receptors (PR) exhibited increased likelihood of response to Tamoxifen. However, some patients with early stage lesions relapse within 10 years. We identified a 5-gene model from 14 candidate expression profiles that improved differentiation of these patients (Kerr & Wittliff, Horm Canc 2:261-71, 2011). Goals are to examine relationships of clinical outcomes of patients whose carcinomas express individual genes and subsets of the models and externally validate their clinical utility. Procedures: De-identified primary breast carcinomas from 342 patients treated with Tamoxifen were used to assess clinical relevance of 14 candidate genes. Laser capture microdissection (LCM) was used previously to isolate carcinoma cells and assess 22,000 genes by microarray. qPCR validated expression of 14 candidate genes. Univariable Cox regression analyses were performed and Kaplan-Meier plots were constructed to assess relationships between either progression-free (PFS) or overall survival (OS) and expression of each gene using R Studio 1.0.143. Relationships of gene expression were segregated by ER/PR (quantified by EIA or radio-ligand binding) with clinical outcomes. SurvExpress evaluated performance externally of individual gene expression and signatures. Results: Univariable Cox regression of microarray results for 14 candidate genes from LCM-procured cancer cells of 247 biopsies without regard to ER/PR status indicated that RERG, ERRB4 and ESR1 were related to PFS while these 3 genes and EGFR and CAXII expression were associated with OS (adjusted p value < 0.30). Validation of individual gene expression of 274 intact tissue sections by qPCR revealed that 4 of these genes (exception of EGFR) as well as PGR, BCL2, SLC39A6, EDG-1, and CD34 were associated with PFS. Expression levels of each of these 9 candidate genes as well as PTGDS, SDF and NQO-1 were independently associated with OS. Kaplan-Meier plots assessed ability of each gene expression level to predict clinical outcomes (PFS/OS). Multivariate Cox regression, performed with backward conditional selection using either microarray data or qPCR results, revealed clinically relevant genes subsets for PFS and OS. SurvExpress, an online tool, was used to externally validate molecular signatures. Conclusions: We externally validated the 5-gene model composed of PGR, BCL2, ERBB4, RERG and CD34 that identified a subset of early stage, ER+ /PR+ breast cancers patients treated with Tamoxifen that exhibited high recurrence rates. ER, PR and HER2 proteins with gene expression were correlated with prediction of clinical outcomes. Clinically relevant molecular signatures identified gene candidates for development of companion diagnostics to their protein products to improve breast cancer management and prediction of risk of recurrence. Citation Format: Zohair Riaz Hameed, Michael W. Daniels, D. Alan Kerr II, James L. Wittliff. Deciphering gene subsets associated with clinical outcomes of early stage breast carcinoma patients treated with Tamoxifen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4622.

Purpose To report the long-term outcomes for women presenting with regional lymph node recurrence after breast conservation treatment with radiotherapy for Stage I and II invasive breast carcinoma. Methods and Materials Of the women with pathologic Stage I and II invasive breast carcinoma treated with breast conservation treatment at the University of Pennsylvania, 29 developed regional nodal recurrence as their first site of failure. An analysis of the patterns of regional nodal recurrence and their prognosis after recurrence was undertaken. The median follow-up from regional nodal recurrence was 5.4 years. Results The pattern of regional nodal recurrence was as follows: 14 (48%) with simultaneous local and axillary recurrence, 7 (24%) with recurrence in the axilla only, 5 (17%) with recurrence in the supraclavicular region only, and 3 (10%) with multiple nodal sites of recurrence. For the entire study group, the 5-, 10-, and 15-year overall survival rate was 70%, 37%, and 28%, respectively. The 10-year overall survival rate for patients with locoregional recurrence was 32% compared with 45% for patients with regional-only recurrence (p = 0.50). The 10-year overall survival rate for patients with axillary recurrence discovered on pathologic examination of the mastectomy specimen was 31% compared with 42% for patients with palpable regional lymphadenopathy (p = 0.83). Conclusion Patients with regional nodal recurrence after breast conservation treatment with radiotherapy for early-stage breast carcinoma are potentially salvageable. The prognosis after regional nodal recurrence was not significantly different when stratified by the presence or absence of simultaneous in-breast recurrence or the method of detection.

SummaryAims and BackgroundThis study of high-dose-rate brachytherapy to the lumpectomy site as the sole radiation presents longer-term results and toxicity of accelerated partial-breast irradiation, using three-dimensional treatment planning.Materials and MethodsFrom March 2002 to July 2004, 25 patients were prospectively included in this study. Six patients were excluded because of definitive histology of lobular carcinoma or positive margin. The median age at the time of treatment was 63.2 years (range 44–77 years). Median follow-up of all patients was 44 months (range 30–53 months) with a minimum follow-up of 30 months. Radiation was delivered using the high-dose-rate remote afterloader VariSource with 192Ir source. The patients received radiation twice a day at least 6 hours apart for a total of 10 fractions over five days with a single dose of 3.4 Gy. The total dose was 34.0 Gy prescribed as a minimum peripheral dose to match or minimally exceed the volume defined by the surgical clips as seen on computed-tomography (CT) scans. Free-hand technique allows conformal placement of the catheters to the shape of the lumpectomy cavity. Side-effects and toxicity were scored using the EORTC/RTOG scale.ResultsAt a median follow-up of 44 months none of the women had developed in-field breast recurrences, one patient had out-of-field recurrences and one patient presented distant metastases. There were no regional nodal recurrences. In each woman, target volume size in cm3 (median 91.3 cm3), dose volume histogram (DVH), and dose homogeneity index (DHI) were calculated. Median DHI was 0.42. Median volume of breast tissue receiving 100% of the prescription dose, V100, was 87%; and V150 48.5%. We noticed two treatment complications: haematoma and abscess in the place of the tumour bed after extirpation. At last follow-up, all patients rated the overall cosmetic outcome as excellent or good.ConclusionsThis method is suitable only for patients with histologically confirmed small tumours (

For the woman with newly diagnosed early stage breast carcinoma undergoing breast conservation treatment, definitive radiation treatment is delivered after breast conservation surgery. While the importance of the technical approach to breast conservation surgery is widely appreciated, the technical skill for radiation treatment is also critical to maximize local-regional control and to minimize toxicity. Recent advances have dramatically improved technical radiation treatment planning and delivery. The radiation treatment technique must be integrated with the surgical procedure performed, the pathology findings, and the systemic treatment delivered. The radiation treatment technique also must coordinate with newer treatment approaches in surgery (e.g., sentinel lymph node biopsy) and systemic therapy (e.g., neoadjuvant systemic therapy, agents with potential cardiac toxicity). To maximize long-term outcome, a sound approach to the technical radiation treatment is an integral component of the combined modality treatment for the patient with early stage breast carcinoma.

BACKGROUND The objective of this study was to assess the cosmesis and toxicities in patients with early-stage breast carcinoma who received treatment with accelerated partial breast irradiation (APBI) using interstitial brachytherapy. METHODS From April 1993 to December 2001, 199 patients with Stage I–II breast carcinoma received breast-conserving therapy with APBI to the tumor bed alone through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines) were assessed at ≤ 6 months, 2 years, and 5 years. RESULTS The median follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all diminished over time. Breast fibrosis and hypopigmentation increased until the 2-year mark and then stabilized. Fat necrosis and telangiectasia increased over time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34% at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all follow-up intervals. Infections (11%) occurred predominantly within the first month after treatment. Good-to-excellent cosmetic outcomes were noted in 95–99% of patients over time; cosmetic results stabilized at 2 years with excellent results increased out to 5 years. CONCLUSIONS APBI with interstitial brachytherapy resulted in mild chronic toxicities, the majority of which diminished or reached a plateau over time. Long-term cosmesis was good to excellent in 95–99% of patients and stabilized at 2 years. Cancer 2006. © 2006 American Cancer Society.

Background Sentinel lymph node biopsy (SLNB) is rapidly becoming the standard of care in the treatment of women with early stage breast cancer. Male breast cancer although relatively rare, has typically been treated with mastectomy and axillary lymph node dissection (ALND). Men who develop breast carcinoma have the same risk as their female counterparts of developing the morbidities associated with axillary dissection. SLNB has been championed as a procedure aimed at preventing those morbidities. We recently have evaluated the role of SLNB in the treatment of men with early stage breast cancer. Methods Among the 18 men treated at the University of Michigan Medical Center for breast cancer from May 1998 to November 2002, 6 were treated with SLNB. Results The mean tumor size was 1.6 cm. The mean patient age was 59.8 years. All of the patients had one or more sentinel lymph nodes identified. Two of the six did not have confirmatory axillary dissection. Three of the six had positive sentinel lymph nodes (50%). Only one of the three patients with a positive sentinel node had more nodes positive. One of the six patients had a positive node on frozen section and underwent immediate complete axillary dissection. This patient had no additional positive nodes. No patients in our series had immunohistochemical studies of the lymph nodes. Conclusions Men with early stage breast carcinoma may be offered the management option of SLNB since in the hands of experienced surgeons it has a success rate apparently equal to that in their female counterparts. J. Surg. Oncol. 2004;86:74–77. © 2004 Wiley-Liss, Inc.

BACKGROUND. in this retrospective data base study, the authors sought to estimate direct costs for bone fractures in women age 65 years with early-stage breast carcinoma and to compare those costs with treatment costs for bone fractures in older women without early-stage breast carcinoma. METHODS. Direct costs for bone fractures in patients with early-stage breast carcinoma, which consist of excess treatment costs for bone fracture and excess costs of long-term care for bone fracture, were evaluated by using the 1997-1998 Standard Analytical File. The statistical significance of the difference in inpatient costs, medical treatment costs, and long-term care admission rates were determined with the t test and the Fisher chi-square test, respectively. RESULTS. For older women with early-stage breast carcinoma, the direct costs for bone fracture were estimated at $45,579, and 57% of those costs came from treating the bone fracture (32% came from inpatient hospital costs, and 25% came from noninpatient hospital costs), 25% came from other excess treatment costs, and 18% came from excess long-term care costs. The women who had early-stage breast carcinoma and sustained bone fracture did not differ significantly from the women without early-stage breast carcinoma who sustained a bone fracture. CONCLUSIONS. Bone fracture was associated with high direct costs in older women with early-stage breast carcinoma. Additional research should include appropriate, incidence-based studies to investigate the potential benefit of an intervention for preventing bone fracture in this increasingly large patient population. (Less)

BACKGROUND The objective of this study was to clarify the prognostic and predictive value of immunoreactivity for the cyclin-dependent kinase inhibitor p27(Kip1) in patients with early-stage breast carcinoma and to investigate its relation with clinicopathologic features and other markers. METHODS Immunoreactivity for p27 protein was analyzed on tumor slides from 461 patients who were enrolled in the International Breast Cancer Study Group (IBCSG) Trial V (median follow-up, 13 years), including 198 patients with lymph node negative disease and 263 patients with lymph node positive disease. Tumors with < 50% immunoreactive neoplastic cells were considered low expressors. Immunoreactivity for p27 was correlated with several clinicopathologic characteristics. Disease free survival (DFS) and overall survival were analyzed according to p27 immunoreactivity and treatment group. RESULTS In the lymph node negative population, decreased p27 immunoreactivity was associated with higher tumor grade (P = 0.001) and HER-2/neu overexpression (P = 0.04). In the lymph node positive population, low p27 expression was associated with higher tumor grade (P = 0.01), low expression of thymidylate synthase (P = 0.001), and higher Ki-67 expression (P = 0.007). DFS was not significantly different according to p27 status in either lymph node negative patients (10-year DFS: low p27 expression, 53% ± 5%; high p27 expression, 55% ± 5%) or in lymph node positive patients (10 year DFS: low p27 expression, 33% ± 4%; high p27 expression, 32% ± 4%). However, in the lymph node negative population, the benefit of one course of perioperative chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil was confined exclusively to patients with tumors that showed reduced p27 immunoreactivity (P = 0.03; test for interaction). CONCLUSIONS This analysis indicates that p27 immunoreactivity has little if any prognostic value in patients with early-stage breast carcinoma. However, these findings suggest that, in patients with breast carcinoma who have negative lymph node status, reduced p27 immunoreactivity is associated with HER-2/neu overexpression and may be predictive of a benefit from the early administration of adjuvant chemotherapy. Cancer 2003;97:1591–600. © 2003 American Cancer Society. DOI 10.1002/cncr.11224

BACKGROUND The current study was performed to compare the value of sentinel lymph node dissection (SND) and axillary lymph node dissection (AND) in improving the utility-adjusted survival for early-stage breast carcinoma patients. METHODS A number needed to treat (NNT) analysis was used to compare SND with AND. In the NNT equation, 1/(SSND − SAND), S is the 5-year utility-adjusted survival. A literature review was performed to estimate 1) the prevalence of axillary lymph node disease for early-stage breast carcinoma, 2) the sensitivity and specificity of SND and AND, 3) the 5-year overall survival as a function of axillary lymph node involvement, 4) the risk of arm lymphedema as a function of the intervention performed, and 5) the utility correction (Uc; impairment of quality of life) for arm lymphedema. RESULTS The NNT method of analysis favored SND over nearly the entire range of parameters with a sign change to a negative value occurring only as Uc becomes very close to unity. This suggests the superiority of the SND approach. Only when there is minimal loss of utility does AND become favored and then only minimally. CONCLUSIONS Compared with AND, SND improves the utility-adjusted survival in patients with early-stage breast carcinoma. This finding is quite robust and was found to remain constant over a range of values for utility and lymph node prevalence. Cancer 2003;97:359–66. © 2003 American Cancer Society. DOI 10.1002/cncr.11081

BACKGROUND Adjuvant tamoxifen is recommended for all women with estrogen receptor-positive breast carcinoma without regard for age. We investigated age-dependent variations in adjuvant tamoxifen prescription patterns in a cohort of women 80 years of age and older. METHODS We studied 92 women diagnosed at four U.S. sites with primary, early-stage breast carcinoma. Each woman consented to a medical record review and participated in two telephone interviews. We compared the proportion of tamoxifen prescriptions received by women 85–92 years of age with those received by women 80–84 years of age. Relative risks (RR) and 95% confidence intervals (95% CI) were generated using generalized estimating equations. Confounding by demographic, disease, and treatment characteristics was assessed. RESULTS Before adjustment, patients 85–92 years of age were 28% less likely to receive a tamoxifen prescription compared with patients 80–84 years of age (RR = 0.72, 95% CI 0.57–0.91). In this sample, patients not prescribed tamoxifen had substantially more comorbidity. After adjusting the crude finding for comorbidity, the RR was 0.74 (95% CI 0.58–0.93). In addition, the oldest patients and those not prescribed tamoxifen were significantly less likely to be married or have living children. After adjusting the crude finding for these two factors, the RR was 0.75 (95% CI 0.59–0.95). There was no confounding by the other demographic, disease, or treatment covariates assessed. CONCLUSION Given the increasing longevity of the oldest old, undertreatment with adjuvant tamoxifen may put older breast carcinoma patients at an increased risk of disease recurrence and breast carcinoma mortality. Cancer 2002;95:2465–72. © 2002 American Cancer Society. DOI 10.1002/cncr.10985

BACKGROUND African-American women have a significantly worse prognosis from breast carcinoma compared with white women, even when the stage at diagnosis is equivalent. The purpose of this study was to analyze racial differences in the treatment (use of breast-conserving surgery and radiation therapy) of women with early-stage breast carcinoma and the resulting effects on survival rates. METHODS Subjects included 10,073 African-American and 123,127 white women diagnosed with Stage I, IIA, or IIB breast carcinoma in the National Cancer Institute's Surveillance, Epidemiology, and End Results program between 1988 and 1998. Comparisons were made by race with treatment, age, hormone receptor status, and stage at the time of diagnosis. Survival analyses were conducted to compare risk of death for African-American and white women while controlling for age, stage, and hormone receptor status. RESULTS Among women diagnosed with early-stage breast carcinoma who receive breast-conserving surgery, African-American women were significantly less likely to receive follow-up radiation therapy in every 10-year age group except in the older than 85 age group. Whether treatment was equivalent or suboptimal, survival for African-American women with early-stage breast carcinoma was significantly worse. However, when treatment was equivalent, the effects of racial differences on survival were significantly less compared with survival associated with suboptimal treatment. CONCLUSIONS Significant racial differences exist in the treatment of women with early-stage breast carcinoma. Public health efforts to eliminate suboptimal treatment would reduce, but not eliminate, racial disparity in survival. Cancer 2002;95:1759–66. © 2002 American Cancer Society. DOI 10.1002/cncr.10827

BACKGROUND. The authors analyzed the outcome of patients with early-stage breast carcinoma after an isolated local recurrence, taking into account initial tumor characteristics and the type of initial treatment and local salvage treatment. METHODS. One hundred five patients were studied who presented with a breast tumor measuring 25 mm and who subsequently developed an isolated local recurrence (breast or chest wall) as the first tumor event. A second series included 335 patients who developed distant metastases as the first event. Cox models that took into account potential prognostic factors were used to estimate the risk of death. First, survival rates were compared after an isolated local recurrence and after a diagnosis of distant metastases; and, second, effects of initial treatments and local or systemic treatments of local recurrences were analyzed. RESULTS. The 10-year survival rate was 56% (95% confidence interval, 45‐ 65%) after an isolated local recurrence compared with 9% (95% confidence interval, 7‐13%) after distant metastasis as the first event. Three independent prognostic factors for the risk of death after local recurrence were identified: histologic tumor grade, patient age at the time of diagnosis with the primary tumor, and disease free interval until recurrence. The type of initial treatment and local salvage treatment did not influence the risk of death. Systemic treatments of local recurrence had different effects according to the patient’s menopausal status. In premenopausal patients, ovarian suppression and chemotherapy significantly decreased the risk of death. In postmenopausal women, systemic treatments did not affect the risk of death. CONCLUSIONS. Isolated local recurrences in patients with early-stage breast carcinoma carry a moderately good prognosis. The outcome of patients is not affected by the type of initial treatment or local salvage treatment. After a local recurrence, ovarian suppression or chemotherapy had a beneficial effect in premenopausal

In this report we describe a cDNA sequence, BS106, identified from Incyte Genomics LifeSeq Expressed Sequence Tag database. A multi-tissue mRNA expression array, northern blots, and RT-PCR assays demonstrate the expression of BS106 in mammary, salivary and prostate glands, but not in other tissue types. BS106 mRNA was detected in 90% of the breast tissues examined. The cDNA encodes a 90-amino acid protein characterized as a small, mucin-like protein based on amino acid composition, extensive O-linked glycosylation, and expression profile. BS106 protein was recombinantly expressed in human embryonic kidney 293 cells and the secreted product was purified from the culture media. Monoclonal antibodies were prepared and used for immunohistochemical analysis of early stage breast cancer. BS106 protein was detected in the vast majority of carcinomas (70-100%) and overexpressed in approximately 30% of the 22 specimens analyzed. BS106 protein was not detected in other solid tumor types including bladder carcinoma, colon carcinoma, endometrial carcinoma, gastric carcinoma, squamous cell lung carcinoma, adenocarcinoma of the lung, ovarian carcinoma, pancreatic and prostatic carcinoma.

Background: Preoperative ultrasound (US) and eventually US-guided fine-needle aspiration cytology (FNAC) of suspicious axillary lymph nodes (ALN) is a standard procedure in the work-up of suspicious breast lesions. Preoperative US FNAC may prevent sentinel node biopsy (SNB) procedure in 24-30% of patients with early stage breast carcinoma. The aim of this study was to evaluate the institutional results of this preoperative diagnostic procedure. Materials and Methods: A total of 182 cases of preoperative FNAC of suspicious ALN where retrieved from the pathology files. The results were compared with the final histology and staging. False negative (FN) FNAC cases were reviewed and possibly missed metastatic cases (2) were immunostained with the epithelial marker AE1/AE3. Results: There were no false positives, whereas 16 cases were FN. In all but one case the FN's represented sampling error. Half of the 16 FN cases in this series were macrometastases. Discussion: About 83% of the preoperatively aspirated cases were N+, indicating that a radiologically suspicious ALN has a very high risk of being metastatic. Preoperative US guided FNAC from radiologically suspicious ALN is highly efficient in detecting metastases. Depending on national guidelines, a preoperative, positive ALN FNAC might help to stratify the patients as to SNB and/or ALN dissection.

BACKGROUND Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue. Cancer 2001;91:1862–9. © 2001 American Cancer Society.

BACKGROUND. Sentinel lymph node (SLN) mapping and biopsy is emerging as an alternative to axillary lymph node dissection (ALND) in determining the lymph node status of patients with early-stage breast carcinoma. The hypothesis of the technique is that the SLN is the first lymph node in the regional lymphatic basin that drains the primary tumor. Non-SLN (NSLN) metastasis in the axilla is unlikely if the axillary SLN shows no tumor involvement, and, thus, further axillary interference may be avoided. However, the optimal treatment of the axilla in which an SLN metastasis is found requires ongoing evaluation. The objectives of this study were to evaluate the predictors for NSLN metastasis in the presence of a tumor-involved axillary SLN and to examine the treatment implications for patients with early-stage breast carcinoma. METHODS. Between June 1998 and May 2000, 167 patients participated in the pilot study of SLN mapping and biopsy at Westmead Hospital. SLNs were identified successfully and biopsied in 140 axillae. All study patients also underwent ALND. The incidence of NSLN metastasis in the 51 patients with a SLN metastasis was correlated with clinical and pathologic characteristics. RESULTS. Of 51 patients with a positive SLN, 24 patients (47%) had NSLN metastases. The primary tumor size was the only significant predictor for NSLN involvement. NSLN metastasis occurred in 25% of patients (95% confidence interval [95%CI], 10-47%) with a primary tumor size less than or equal to 20 mm and in 67% of patients (95%CI, 46-83%) with a primary tumor size > 20 mm (P = 0.005). The size of the SLN metastasis was not associated significantly with NSLN involvement. Three of 7 patients (43%) with an SLN micrometastasis (< 1 mm) had NSLN involvement compared with 38 of 44 patients (48%) with an SLN macrometastasis (greater than or equal to 1 mm). CONCLUSIONS. The current study did not identify a subgroup of SLN positive patients in whom the incidence of NSLN involvement was low enough to warrant no further axillary interference. At present, a full axillary dissection should be performed in patients with a positive SLN. (C) 2001 American Cancer Society.

Chemotherapy has been shown to be efficacious in women with breast carcinoma in numerous clinical trials over the past several decades.1–3 However, the efficacy of chemotherapy and guidelines for its use vary by tumor stage and patient age.4–10 In the 1985 National Institutes of Health (NIH) consensus statement, combination chemotherapy was considered as the standard of care for premenopausal women and postmenopausal women younger than 70 years with operable breast carcinoma with positive lymph nodes and for those with negative lymph nodes with high-grade tumor histology or negative hormone receptors.4 This recommendation was essentially repeated in the 1990 and 2000 consensus conferences, with the additional statement that lymph node negative tumors greater than 1 cm should be considered for adjuvant chemotherapy.5,8 These consensus recommendations noted the lack of evidence of efficacy of adjuvant chemotherapy in women age 70 years and older. Meta-analyses have shown decreasing benefit from adjuvant chemotherapy with increasing age, though few women age 70 years and older have been enrolled in such trials.1–3 Accordingly, there are no clear recommendations for adjuvant chemotherapy in women age 70 years and older. For women with more advanced tumor (Stages III and IV), systemic therapy (chemotherapy or hormonal therapy or both, depending on hormonal receptor levels) was recommended as primary therapy in both premenopausal and postmenopausal women.10 There is little information available on the actual use of chemotherapy and how closely this use mirrors consensus recommendations. The previous reports on the prevalence of chemotherapy use have produced conflicting results.11–21 A series of the national hospital-based surveys of breast carcinoma in the United States, organized by the American College of Surgeons,12,13 reported that 16.4% of women of all ages with local to distant breast carcinoma had used chemotherapy in 1976, and it increased to 22.7% in 1981. By 1991, 46.6% of women received chemotherapy or tamoxifen (no specific data given on the use of chemotherapy only).12 The prevalence of chemotherapy use in 17 community hospitals across the nation in 1982 in women age 65–74 years was 55% for regional stage and 49% for distant stage.11 In contrast, among women age 65 or older with early stage breast carcinoma diagnosed in a large health maintenance organization (HMO), only 13% of them received chemotherapy in 1993–1994.14 This study was conducted to assess temporal trends in the use of chemotherapy among women age 65 years and older who received a diagnosis of breast carcinoma from 1991 to 1996, using the SEER cancer registry cases linked with Medicare claims. We hypothesized that, given the relative stability of consensus conference recommendations on chemotherapy use during this period, the patterns of use would more closely approximate consensus recommendation over time. Because no clear recommendations exist for women age 70 and older, we expected to see a closer approximation to consensus conference recommendations among women age 65–69 years than in older women.

BACKGROUND Sentinel lymph node biopsy (SLNB) is now a widely implemented technique for evaluating the axilla in women with early stage breast carcinoma. Men who develop breast carcinoma are at similar risk as their female counterparts of developing the morbidities related to axillary dissection. SLNB is aimed at preventing these morbidities. In this study, the authors evaluated the role of SLNB in the treatment of men with early stage breast carcinoma. METHODS Among the 1692 patients who underwent SLNB at the Memorial Sloan-Kettering Cancer Center, 16 men with breast carcinoma were identified. The charts and records of these 16 patients were reviewed retrospectively. RESULTS The mean patient age was 57.2 years. The mean tumor size was 1.3 cm. In 15 of 16 patients (93.75%) and in all patients with T1 tumors, one or more sentinel lymph nodes were successfully identified. SLNB failed in one patient, who had a T2 tumor (3 cm). Ten of the 15 patients had negative sentinel lymph nodes (66.7%). Four of these patients had no additional lymph nodes removed, whereas six patients had additional lymph nodes removed, all of which were negative. Two patients (13.3%) had positive sentinel lymph nodes on frozen-section analysis and underwent immediate completion axillary dissection: Both had additional positive lymph nodes. Three patients (20.0%) had positive sentinel lymph nodes on further sectioning or immunohistochemistry, and two patients underwent completion axillary dissection: Neither patient had additional positive lymph nodes. The third patient had one immunohistochemically positive lymph node and did not undergo completion axillary dissection. CONCLUSIONS SLNB for patients with breast carcinoma was as successful in men as it has been shown to be in women and may be offered as a management option to men with early stage breast carcinoma by surgeons who are experienced with the technique. Cancer 2001;91:319–23. © 2001 American Cancer Society.

BACKGROUND Studies that prospectively and simultaneously evaluate, within the first year of diagnosis, the impact of surgery and chemotherapy on quality of life (QOL) of younger women (60 years or younger) with early stage breast carcinoma are limited. METHODS Quality of life of 103 women who had surgery (lumpectomy, 49; mastectomy, 54) approximately 1 month before the start of the study was evaluated at baseline and again after 5 months. Thirty-two women received chemotherapy during the study. RESULTS Over time, subjects reported improvement in body image and physical, emotional, and functional well-being (P < 0.001). They were less bothered by swollen/tender arms and worried less about risk of cancer to family members (P < 0.001). However, satisfaction with sex life, social support, and social/family well-being declined (P < 0.001). In the period closer to surgery, women with mastectomy reported poorer body image (P = 0.001) and worse functional (P = 0.08) and physical well-being (P = 0.10). Women with lumpectomy worried more about the effects of stress on their illness (P < 0.01) and had lower emotional well-being (P = 0.06). By 6 months after surgery, the two groups reported similar QOL scores. Chemotherapy had a negative impact on women's sexual functioning (P = 0.01) and their physical well-being (P = 0.09). Women who received chemotherapy also reported more shortness of breath (P = 0.07). Post hoc analysis showed that women with breast reconstruction had higher emotional well-being at baseline than those with lumpectomy (P = 0.001) and mastectomy alone (P < 0.01). CONCLUSIONS Younger women with breast carcinoma could experience a range of adjustment problems at various points in the treatment cycle. Interventions that would help reduce the negative impact of treatment on QOL need to be designed and integrated into routine clinical practice. Cancer 2001;92:1288–98. © 2001 American Cancer Society.

BACKGROUND The objective of the current study was to evaluate the effectiveness and morbidity of primary axillary radiotherapy in breast-conserving therapy for postmenopausal, clinically axillary lymph node negative patients with early stage breast carcinoma. METHODS Between 1983–1997, 105 patients with clinically negative axillary lymph nodes and breast carcinoma were treated with wide local excision followed by radiotherapy to the breast, and axillary and supraclavicular lymph node areas. Adjuvant treatment with tamoxifen was given to 75 patients. The median follow-up of patients still alive was 41 months (range, 8–137 months). Fifty-five patients with no evidence of disease at last follow-up were examined prospectively with respect to late functional damage. RESULTS The mean age of the patients was 64 years. Three patients developed a local recurrence. No isolated axillary lymph node recurrence was observed. In two patients, axillary recurrence was accompanied by distant metastases. The 5-year disease free interval and the overall survival were 82% (standard error [SE], 6%) and 83% (SE, 6%), respectively. In five patients, arm edema was reported and impaired shoulder function was reported in seven patients. Prospectively scored, arm edema was reported subjectively by the patient in 4% and objectively measured in 11% of cases. Impaired shoulder function was reported subjectively in 35% and objectively measured in 17% of cases. No brachial plexus neuropathy was noted. CONCLUSIONS Primary axillary radiotherapy for postmenopausal women with clinically lymph node negative, early stage breast carcinoma was found to result in low axillary lymph node recurrence rates with only limited late complications. Therefore, primary axillary radiotherapy should be considered as axillary treatment in selected patients as an alternative to axillary lymph node dissection. Cancer 2000;88:1633–42. © 2000 American Cancer Society.

BACKGROUND Induction chemotherapy (IC) has become the standard of care for locally advanced breast carcinoma, frequently downstaging both the primary tumor and the axilla, and making patients eligible for less invasive surgical procedures. The usefulness of IC in earlier stage operable breast carcinoma is now being considered. METHODS This study involved a subset of 129 patients from a series of 174 with T2–3, N0–1, M0 or T1, N1, M0 breast carcinoma (Stage IIA, IIB, or IIIA ) who were registered in a prospective IC trial using paclitaxel or a combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC). The subset included patients who had received no preoperative radiation therapy but had completed 3–5 cycles of induction chemotherapy and had undergone a Level I–II axillary lymph node dissection. The objective was to evaluate the effectiveness of induction chemotherapy with paclitaxel or FAC in downstaging the primary tumor and axillary metastases in these early stage breast carcinoma patients. RESULTS The median initial tumor size was 4 cm (range, 0.6–10.0); after IC, tumor size was downstaged to 1.6 cm (range, 0.0–7.0) (P < 0.0001). Clinical response to IC was complete in 24% of patients and partial in 36%. Primary tumor shrinkage was similar with paclitaxel and FAC. Among patients clinically classified as N1, 34% became histologically negative and 38% had only 1–3 positive lymph nodes after induction chemotherapy. CONCLUSIONS IC with paclitaxel or FAC resulted in effective downstaging of primary tumors and axillary metastases in patients with Stage IIA, IIB, and IIIA breast carcinoma. However, a significant proportion of patients still had residual but low volume microscopic disease; such disease status may allow minimally invasive surgical approaches to locoregional therapy. Cancer 2000;88:1417–24. © 2000 American Cancer Society.

BACKGROUND Thirty percent of lymph node negative patients with operable breast carcinoma experience disease recurrence within 10 years. Retrospective serial sectioning of axillary lymph nodes has revealed undetected metastases in 9–30% of these patients. These occult metastases have been shown to have an adverse effect on survival. Serial sectioning (SS) is impractical for all axillary lymph nodes harvested from Levels I and II, but it is feasible if applied only to sentinel lymph nodes. METHODS Sentinel lymph nodes from 52 patients with invasive breast carcinoma were cut at 2 mm intervals, fixed in 10% formalin, and embedded in paraffin. Sections were taken from the blocks, stained with hematoxylin and eosin (H & E), and compared with cytokeratin-stained sections taken at 0.25 mm intervals throughout the entire blocks. RESULTS Tumor metastases were found in 6 patients (12%) when the sentinel lymph nodes were sectioned at 2 mm intervals and stained with H & E, compared with 30 patients (58%) when the same lymph nodes were serially sectioned at 0.25 mm intervals and stained with cytokeratin. Of 24 patients whose metastases were detected by SS and cytokeratin staining, 12 had isolated tumor cells and 12 had colonies of several thousand malignant cells. CONCLUSIONS Routine histologic examination of axillary lymph nodes, including sentinel lymph nodes, in cases of breast carcinoma significantly underestimates lymph node metastases. This deficiency may be overcome by SS of the entire lymph nodes and staining with a specific monoclonal antibody. The percentage of patients found to have colonies of cells that were missed by routine sectioning corresponds closely to the percentage of “lymph node negative” patients who would be expected to relapse. The true clinical significance of these occult metastases will be determined by long term follow-up. [See editorial on pages 905–7, this issue.] Cancer 1999;86:990–6. © 1999 American Cancer Society.

BACKGROUND Controversy exists concerning the roles of mammography and physical examination in the detection of local recurrence after conservation therapy for breast carcinoma. In addition, the prognostic factors for and optimal treatment of patients with local recurrence are uncertain. METHODS At eight radiotherapy institutes, two cancer institutes, and one surgical clinic in the Netherlands, regular follow-up of patients who underwent breast conservation therapy between 1980 and 1992 identified 266 patients with local recurrence in the breast. These patients exhibited no clinical signs of distant metastases at the time of diagnosis of the local recurrence. Data on the method of detection were available for 189 patients (72%). Local recurrence was diagnosed by mammography alone in 47 cases (25%). Of all patients, 85% underwent salvage mastectomy, 8% underwent local excision, 4% received systemic treatment only, and 3% remained untreated. Specimens of the primary tumor were available for review from 238 of the 266 patients (89%). RESULTS Local recurrences detected by mammography alone were smaller than those detected by physical examination (P = 0.04). At 5 years from the date of salvage treatment, the overall survival rate for all 266 patients was 61% (95% confidence interval [CI], 55–67%), and the distant recurrence free survival rate was 47% (95% CI, 40–53%). For the 25 patients with noninvasive recurrence, these figures were 95% and 94%, respectively. Skin involvement, the extent of recurrence (≤10 mm vs. >10 mm), and both lymph node status and histologic grade of the primary disease were strong predictors for distant metastases in patients with invasive recurrence. CONCLUSIONS Patients with invasive local recurrence more than 1 cm in size are at a substantial risk for distant disease. The better distant disease free survival for patients with recurrence measuring 1 cm or less may indicate that early detection can improve the treatment outcome. Recurrence with skin involvement should be considered generalized disease. Cancer 1999;85:437–46. © 1999 American Cancer Society.

BACKGROUND The National Cancer Data Base (NCDB), a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society, is a cancer management and outcome data base for health care organizations. It provides a comparative summary of patient care that is used by participating hospitals and communities for self-assessment. The most current (1995) data are described herein. METHODS Since 1989, seven calls for data have been issued, yielding reports on a total of 240,031 breast carcinoma patients for the years included in this analysis. A total of 1849 hospital cancer registries responded to at least 1 of the calls for data. RESULTS A continuous improvement in care was reported. By 1995, 45.8% (nearly one-half) of breast carcinoma patients were diagnosed early as Stage 0 or I, and early stage patients (Stage 0 or I) were most often treated with partial mastectomy (in 58% of cases). Favorable 10-year relative survival rates for Stage 0 (95%) and Stage I (88%) breast carcinoma patients were reported. Patients who were presumed to be Stage I and were not selected for axillary dissection had poorer survival. Survival differences were reported for different treatment groups within individual stage strata. Over the 10-year observation period, fewer patients from lower-income neighborhoods were diagnosed with early stage breast carcinoma. In general, the annual relative survival rate remained constant over the 10-year observation period (with no plateau after 5 years) within each stage and for all stages combined. CONCLUSIONS Improvements in diagnosis and treatment during the period 1985-1995 were demonstrated by these data. The NCDB breast carcinoma data are appropriate norms for formal quality assurance purposes, such as those specified by the Standards of the Commission on Cancer published by the American College of Surgeons Commission on Cancer. Cancer committees and other clinicians working within the hospital setting should assess and compare stage distribution, stage specific treatment patterns, and the correlations between the outcomes of patients and both disease stage and treatment. Cancer 1998;83:1262-1273. © 1998 American Cancer Society.

BACKGROUND In response to the importance of early stage breast carcinoma as a public health concern and to the complexity of the clinical literature devoted to treatment of the disease, the National Institutes of Health has held a series of Consensus Development Conferences on the treatment of early stage breast carcinoma. The authors assessed compliance with standards of care for women treated in two states. METHODS The authors identified patients diagnosed at 18 randomly selected hospitals (N = 1514) in Massachusetts and at 30 hospitals (N = 1061) in Minnesota. They collected data from medical records, patients, and their surgeons to assess compliance with four indicators of quality of care: radiation therapy after breast-conserving surgery, axillary lymph node dissection, chemotherapy for premenopausal women with positive lymph nodes, and hormonal therapy for postmenopausal women with positive lymph nodes and positive estrogen receptor status. RESULTS Rates of compliance for 3 of the 4 standards of care were > 80% in both states. Only the rate for hormonal therapy for postmenopausal women was low ( 90% in both states. CONCLUSIONS In the states studied, practice appears to be consistent with the results of national consensus conferences and clinical trials regarding the treatment of early stage breast carcinoma. For practices demonstrated to be associated definitively with better outcomes (for example, chemotherapy for premenopausal women with positive lymph nodes) or to be important with respect to prognosis (axillary lymph node dissection) high rates of compliance were observed. Cancer 1998;83:302-309. © 1998 American Cancer Society.

BACKGROUND There are conflicting reports regarding whether focally positive surgical margins influence tumor control in breast-conservation therapy. The authors have evaluated the relation between positive surgical margins on tumor control and whether the number of positive margins affects tumor control in patients undergoing reexcision lumpectomy. METHODS From 1978 to 1994, 453 American Joint Committee on Cancer Stage I/II breast carcinoma patients were treated at Thomas Jefferson University Hospital with breast conservation therapy. Patients underwent excisional biopsy and margin sampling with shaved biopsies of the tumor cavity. The entire breast received 45 grays (Gy) with a 20-Gy iridium-192 implant or an electron boost. Eighty-six patients had microscopically positive margins (19%), and the remainder had confirmed negative margins. The median follow-up time was 45 months. RESULTS Local tumor control rates for patients with negative margins at 5 and 10 years were 94% and 87%, respectively, compared with 86% and 69%, respectively, for those patients with positive margins (P = 0.005). The disease free survival rates for the negative margin group at 5 and 10 years were 91% and 82%, respectively, compared with 76% and 71%, respectively, for the positive margin group (P = 0.001). Overall survival rates for patients with negative margins at 5 and 10 years were 95% and 84%, respectively, compared with 87% and 78%, respectively, for those with positive margins (P = 0.047). When comparing the negative margin group with the positive margin group, there was no significant difference in local tumor control (P = 0.12). However, women with two or more positive margins had an inferior local tumor control compared with those women with negative margins (P = 0.002). CONCLUSIONS Patients with positive margins have a higher risk for local failure and worse survival when undergoing breast conservation therapy. Inferior local tumor control was noted in those patients with two or more positive margins. Cancer 1998;82:2212-2220. © 1998 American Cancer Society.

BACKGROUND The use of adjuvant tamoxifen to treat postmenopausal breast carcinoma patients as an adjunct to primary surgery is well established. The current study reports the long term results for a low risk stratum in a randomized trial of adjuvant tamoxifen. The main focus of this analysis was to determine whether tamoxifen would result in a reduced local failure rate for lymph node negative, postmenopausal patients treated with breast-conserving surgery and postoperative radiotherapy. METHODS The study population included 432 lymph node negative, postmenopausal patients with invasive breast carcinoma (classified as T1-T2) who underwent breast-conserving surgery followed by radiotherapy in Stockholm during the period 1976-1990. The patients constituted a separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19 years). RESULTS At 10 years, the overall survival was 90% for the tamoxifen group and 88% for the control group. The event free survival at 10 years was 80% for the tamoxifen group and 70% for the control group (P = 0.03). Tamoxifen reduced the overall rate of ipsilateral (hazard ratio = 0.4, 95% confidence interval [CI] = 0.2-0.9, P = 0.02) and contralateral breast tumor recurrences (hazard ratio = 0.4, 95% CI = 0.1-1.1, P = 0.06). Trends toward a reduced number of distant metastases (hazard ratio = 0.6, 95% CI = 0.3-1.2, P = 0.1) and deaths due to breast carcinoma (hazard ratio = 0.5, 95% CI = 0.2-1.2, P = 0.1) also were observed. CONCLUSIONS The addition of tamoxifen to radiotherapy for postmenopausal, lymph node negative breast carcinoma patients treated with breast-conserving surgery resulted in a reduced rate of ipsilateral and contralateral breast tumor recurrences. The avoidance of salvage mastectomies, reexcisions, and new contralateral malignancies justifies the use of tamoxifen even in the treatment of patients with a 10-year survival rate of 90%. [See editorial on pages 2090-2, this issue.] Cancer 1998;82:2204-2211. © 1998 American Cancer Society.

BACKGROUND The ability of screening mammography programs serving women of different socioeconomic status (SES) to diagnose early stage breast carcinoma in a comparably effective fashion has been questioned. METHODS Results of screening 50,653 women of lower SES were compared with those of screening 45,923 more socioeconomically advantaged women during the same period in New York State. Results were compared with those reported for the general population to the New York State cancer registry. RESULTS Additional workup was required for approximately 12% of the women in each group. Although more women of lower SES underwent biopsy, the positive predictive value of a biopsy recommendation was almost the same for the two populations (27% for women of higher SES vs. 25% for women of lower SES). Among women with breast carcinoma, ductal carcinoma in situ was diagnosed in 27% of more affluent women and 15% of women of lower SES, a considerable improvement from the 10% rate of diagnosis in the general population in New York State. Minimal cancers accounted for 54% of those diagnosed in more affluent women and at least 31% of those diagnosed in women of lower SES. CONCLUSIONS Screening mammography programs can be effective for women of lower SES and can be conducted as efficiently as they are for more affluent women. Differences in diagnosis of small cancers in the two groups reported in this article may reflect differences in age and patterns of prior screening experience in the two populations. Cancer 1998;82:1692-7. © 1998 American Cancer Society.

BACKGROUND Although increasing rates of breast carcinoma incidence have been observed in Asian countries, appropriate strategies for detecting early stage breast carcinoma in such communities have been difficult to formulate, particularly because no large population screening trial specifically involving Asian women has been reported. The objective of this study was to evaluate the effectiveness and quality of mammography as a screening technique for Singaporean women, who are predominantly Chinese. METHODS In this prospective study, 166,600 women in Singapore ages 50-64 years were randomized to either 2-view mammography without physical examination (67,656) or observation (97,294, controls) over 2 years. RESULTS Of these women, 28,231 (41.7%) responded and were screened; they were more likely to be married, have more formal education, be working, be Chinese, and be in a higher socioeconomic group (P < 0.001 for all variables). To assess for response bias that could affect outcome, results were also evaluated for nonrespondents (n = 39,425). The incidence rate of cancers among nonrespondents (1 per 1000 woman-years) was less than the 1.3 in women not invited to have screening (P = 0.03, relative risk [RR], 1.3; 95% confidence interval [CI], 1.0-1.7). However, cancers arising from nonrespondents did not differ significantly in stage distribution when compared with cancers within the control group. For every 1000 women screened, 4.8 cancers were detected. The prevalence ratio (the number of cancers detected per 1000 women at first screening divided by the corresponding incidence rate in controls per year) was 3.6 for screened women and 2.4 for women invited to have screening. The majority of cancers detected through screening were early stage, with 64% as either ductal carcinoma in situ (26%) or Stage I disease (38%) and was significantly more than the corresponding 26% in women not invited to have screening (P < 0.001). When only invasive cancers were considered, screened women still had more early cancers, with 65% having no lymph node involvement, compared with 47% in the group not invited to have screening (P = 0.001; RR, 1.4; 95% CI, 1.2-1.7). Women who were screened had half the risk of having Stage II or later cancers (P < 0.0001; RR, 0.5; 95% CI, 0.4-0.7) when compared with women not invited to have screening. This higher detection rate of early cancers through screening was accomplished with acceptable recall rates of 8% for further mammographic films or physical examination and a biopsy rate of 1.0% (10 per 1000 women screened). The interval cancer rate was 2.1 per 10,000 women screened in the first year of follow-up. CONCLUSIONS These positive results of intermediate measures suggest that, in Asian communities, screening mammography could be an important modality for detecting early stage breast carcinoma. However, the low compliance rates suggest that health education efforts must focus on issues related to acceptability if such programs are to succeed. Cancer 1998;82:1521-28. © 1998 American Cancer Society.

BACKGROUND Prospective randomized trials and retrospective reviews from academic centers have documented the success of breast-conserving therapy (BCT) for patients with early stage breast carcinoma. The authors retrospectively reviewed the outcome of BCT for early stage breast carcinoma to determine the success of BCT at the study institution, a 1000-bed community hospital. METHODS Between January 1980 and December 1987, 400 cases of Stage I and II breast carcinoma were managed with BCT at the study institution. All patients were treated with an excisional biopsy. The axilla was surgically staged in 383 patients (96%). Postoperative treatment was composed of 45-50 gray (Gy) external beam irradiation to the whole breast and a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up of the 292 surviving patients is 118 months. RESULTS At last follow-up, there were 37 local recurrences for 5- and 10-year actuarial rates of 4% and 10%, respectively. Clinical, pathologic, and treatment-related factors were analyzed for an association with local recurrence. On univariate analysis, patient age ≤ 35 years and positive surgical margins were associated with an increased risk of local recurrence. On multivariate analysis, only patient age ≤ 35 years remained significant. The 10-year actuarial regional recurrence rate was 5%. The 10-year actuarial cause specific survival rate was 91% and 69% for Stage I and II patients, respectively. CONCLUSIONS BCT for patients with early stage breast carcinoma in a community hospital setting produces excellent results comparable to contemporary series reported from academic institutions and multiinstitution trials. Cancer 1998;82:127-33. © 1998 American Cancer Society.

Understanding why older women with breast carcinoma do not receive definitive treatment is critical if disparities in mortality between younger and older women are to be reduced. With this in mind, the authors studied 302 women age > or =55 years with early stage breast carcinoma. Data were collected from surgical records and in telephone interviews with the women. The main outcome was receipt of definitive primary tumor therapy, defined either as modified radical mastectomy or as breast-conserving surgery with axillary dissection followed by radiation therapy. The majority (56%) of the women underwent breast-conserving surgery and axillary dissection followed by radiation therapy. After statistical control for four variables (comorbidity, physical function, tumor size, and lymph node status), patients' ages, marital status, and the number of times breast carcinoma specialists discussed treatment options were significantly associated with the receipt of definitive primary tumor therapy. The authors concluded that when older women have been newly diagnosed with breast carcinoma and there is clinical uncertainty as to the most appropriate therapies, patients may be better served if they are offered choices from among definitive therapies. In discussing therapies with them, physicians must be sensitive to their fears and concerns about the monetary costs and functional consequences of treatment in relation to the expected benefits.

Objective: To investigate the effect of breast-conservation therapy in early stage breast cancer. Methods: A total of 234 early stage breast carcinoma patients received breast conserving treatment in our hospital. After the operation, they underwent adjuvant chemotherapy and radiotherapy. All of these patients desired to preserve their breasts. Results: After median follow-up of 29.46 months (range from 3 to 100 months), 3 cases had local relapse and 8 cases had distant metastasis. The overall survival rate of 5 year was 96.7%, and the disease free survival rate of 5 year was 87.85%. Conclusion: For early stage breast carcinoma patients, classic quadrantectomy, axillary dissection and post-operative adjuvant chemotherapy and radiotherapy lead to excellent local control and good survival.

Background Aberrant DNA methylation of regulatory genes has frequently been found in human breast cancers and correlated to clinical outcome. In the present study we investigate stage specific changes in the DNA methylation patterns in order to identify valuable markers to understand how these changes affect breast cancer progression. Methods Quantitative DNA methylation analyses of 12 candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B, PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast cancer tissue samples from DCIS to invasive tumors stage I to IV. Results Significant differences in methylation levels between the DCIS and invasive stage II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in late stage compared to the early stage breast carcinoma. Z-score analysis revealed significantly lower methylation levels in DCIS and stage I tumors compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B, FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had significantly lower overall methylation levels compared to tumors with wild type TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed that HER2 positive tumors had significantly higher z-scores of methylation compared to the HER2 negative tumors. Univariate survival analysis identifies methylation status of PPP2R2B as significant predictor of overall survival and breast cancer specific survival. Conclusions In the present study we report that the level of aberrant DNA methylation is higher in late stage compared with early stage of invasive breast cancers and DCIS for genes mentioned above.

A determination of circulating tumor cell (CTC) effectiveness for prediction of progression-free survival (PFS) and overall survival (OS) was conducted as an adjunct to standard treatment of care in breast cancer management. Between November 2008 and March 2009, 22 metastatic and 12 early stage breast carcinoma patients, admitted to Ankara Oncology Training and Research Hospital, were included in this prospective trial. Patients’ characteristics, treatment schedules and survival data were evaluated. CTC was detected twice by CellSearch method before and 9-12 weeks after the initiation of chemotherapy. A cut-off value equal or greater than 5 cells per 7.5 ml blood sample was considered positive. All patients were female. Median ages were 48.0 (range: 29-65) and 52.5 (range: 35-66) in early stage and metastatic subgroups, respectively. CTC was positive in 3 (13.6%) patients before chemotherapy and 6 (27.3%) patients during chemotherapy in the metastatic subgroup whereas positive in only one patient in the early stage subgroup before and during chemotherapy. The median follow-up was 22.0 (range: 21-23) and 19.0 (range: 5-23) months in the early stage and metastatic groups, respectively. In the metastatic group, both median PFS and OS were significantly shorter in any time CTC positive patients compared to CTC negative patients (PFS: 4.0 vs 14.0 months, Log-Rank p=0.013; and OS: 8.0 months vs. 20.5 months, Log-Rank p

Several molecular tests have been developed to estimate risk of distant recurrence and help clinical decision-making regarding adjuvant chemotherapy in patients with early stage breast carcinoma. Both Oncotype DX, a 21-gene expression profile, and Mammostrat, an immunohistochemistry-based assay, are validated to stratify patients into groups with low, intermediate and high risk of distant recurrence. However, they have not been compared head-to-head and little data are available regarding their correlation with clinicopathologic tumor features. In this study, we compared the clinicopathologic tumor features with risk estimations by Oncotype DX and Mammostrat in 106 low-grade estrogen receptor (ER)-positive breast carcinomas. Double immunohistochemical stain for pancytokeratin and Ki-67 was performed to assess cell proliferation in cancer vs stromal/inflammatory cells. Tumors showing intermediate/high risk by Oncotype DX, but not by Mammostrat, showed increased stromal cellularity, presence of inflammatory cells and increased proliferation in stromal/inflammatory cells. Discrepant cases showing intermediate/high risk by Oncotype DX but low risk by Mammostrat were associated with increased stromal cellularity, presence of inflammatory cells and increased proliferation in stromal/inflammatory cells, compared with concordant cases showing low risk by both assays. Our results suggest that low-grade ER-positive breast carcinomas with increased stromal/inflammatory cell proliferation may show an apparent increased risk of distant recurrence as assessed by Oncotype DX, which uses RNA extracted from a mixture of tumor and stromal/inflammatory cells in the assay. Mammostrat, which examines cancer cells only, may provide a better estimation of likely tumor behavior in a subgroup of low-grade breast carcinomas.

The aim of this study was to analyze the effect of the type of local surgical treatment on survival in young women aged less than 40 years with T1 breast cancer. We analyzed data from 3,512 patients aged ≤40 years old who were diagnosed with T1 breast cancer from the Korean Breast Cancer Registry database between January 1988 and December 2006 and underwent either breast-conserving therapy (BCT) or mastectomy. The overall survival (OS) and breast-cancer-specific survival (BCSS) were compared between BCT and mastectomy. Of the 3,512 patients analyzed, 1,951 (55.6 %) underwent BCT, and 1,561 (44.4 %) underwent mastectomy. The median follow-up period was 111.0 (79.0–131.5) months. Overall, the 10-year OS rates for BCT and mastectomy were 95 and 92.1 %, respectively (p = 00004), and the 10-year BCSS rates for BCT and mastectomy patients were 96.9 and 94.9 %, respectively (p = 0.12). In node-negative patients, no significant difference was observed in either the OS (adjusted hazard ratio [HR] 1.072; 95 % CI, 0.750–1.5332, p = 0.704) or BCSS (adjusted HR 0.988; 95 % CI, 0.620–1.574, p = 0.960) rate between the BCT and mastectomy groups. In node-positive patients, no significant difference was observed in the OS (adjusted HR 1.634; 95 % CI, 0.982–2.272, p = 0.59) and BCSS (adjusted HR 1.410; 95 % CI, 0.755–2.633, p = 0.281) rates between the BCT and mastectomy groups. In this large, population-based analysis of young women with T1 breast cancer, the OS and BCSS were not different between BCT and mastectomy.

Background Clinical studies agree that obesity worsens the prognosis of breast carcinoma in both pre- and postmenopausal women. There is considerable evidence that free estrogen levels are raised in obese women, especially in those with abdominal (visceral) obesity and hyperinsulinemic insulin resistance. It has been postulated that estrogen may synergize with the concomitants of hyperinsulinemia in stimulating breast carcinoma growth. Reduction of estrogen and insulin levels may slow this growth. Methods A current clinical trial in the U.S. is examining the effect of dietary fat reduction on recurrence and survival rates after primary treatment of early stage breast carcinoma in postmenopausal women. Recent research suggests that a high fiber/fat ratio in the diet and regular physical exercise may help to reduce estrogen and insulin levels. Regular exercise may also help to maintain long term weight loss. Results A second-generation trial is proposed of a high fiber, low fat diet associated with regular physical exercise in women with early breast carcinoma. Changes in circulating levels of estrogen and insulin will be monitored in relation to timing of tumor recurrence and second primary breast carcinoma rates. Weight and fat distribution will be monitored in relation to measurements of dietary compliance. Conclusions Breast carcinoma patients wishing to change their lifestyle are likely to benefit from a higher dietary fiber/fat ratio combined with regular physical exercise. If the trial shows an improved prognosis from intervention correlated with changes in biomarkers, a similar trial model could be used to identify specific fiber supplements, micronutrients, and exercise regimens that may improve survival rates in patients with breast carcinoma.

BACKGROUND Although histologic grade has previously been described as a predictor of distant failure, it is uncertain whether histologic grade should be used to decide which patients should undergo axillary lymph node dissection and whether grade should be considered as a selection factor for breast-conserving therapy. METHODS The authors retrospectively analyzed data from 1081 patients with American Joint Committee on Cancer Stage I or II infiltrating ductal carcinoma treated with breast-conserving therapy at the Joint Center for Radiation Therapy between 1970 and 1986. All patients had pathology slides reviewed by one of two study pathologists. Using the Elston modification of the Bloom-Richardson grading system, patients were divided by histologic grade into 3 groups (219 with Grade I, 482 with Grade II, and 380 with Grade III). The median follow-up time for 716 survivors was 134 months. The incidence of various pathologic features was examined with respect to histologic grade. In addition, the 10-year crude rates of failure (by first site) were examined as they related to grade. A polychotomous logistic regression model was used to determine the effect of grade on local and distant failure. RESULTS High grade tumors tended to be larger, to exhibit more mononuclear cellular reaction and necrosis, and were more likely to be estrogen receptor negative. Patients with high grade tumors were also younger than those with lower grade tumors. The incidence of an extensive intraductal component and lymphatic vessel invasion did not vary significantly by histologic grade. The incidence of pathologic lymph node metastases also did not vary by grade, even when stratified by tumor size. In both univariable and multivariable analyses, the 10-year crude rate of local recurrence was not related to histologic grade (P = 0.44). Distant recurrence rates, however, were significantly higher as grade increased (P = 0.002). CONCLUSIONS Higher histologic grade predicted an increased incidence of distant recurrence, but not a greater likelihood of axillary lymph node metastases or local recurrence after breast-conserving therapy. The authors conclude that grade should not be used to make decisions regarding local management. Cancer 1996;78:1426-31.

BACKGROUND There appears to be a growing movement in favor of core needle biopsy (CNB) over fine-needle aspiration (FNA) cytology in detecting breast carcinoma in women. The authors compared the sensitivity and specificity of these two methods in patients who presented to The University of Texas M. D. Anderson Cancer Center for evaluation of a palpable breast mass. METHODS One hundred and twenty-four women (mean age, 51 years; range, 28-86 years) with a clinically suspicious palpable mass (mean size, 4.4 cm; range, 1-12 cm) underwent concurrent FNA and CNB. For the FNA, an average of three needle passes were made. FNA was followed by three CNBs using the Bard Monopty needle. CNB samples were submitted for frozen section to determine adequacy, and an additional three cores were performed if the first batch was deemed inadequate. All patients ultimately had histologic confirmation of their neoplasms either by the core needle procedure or by definitive open surgical biopsy. Features of cases with discrepant diagnoses were examined in relation to tumor size and histologic type. RESULTS Specificity of both FNA and CNB was 100%. The sensitivity in detecting a malignant neoplasm was higher for FNA than for CNB (97.5% vs. 90%, P < 0.004). CONCLUSIONS In our experience, FNA of palpable breast lesions is a more sensitive method for the detection of carcinoma regardless of tumor type, size, or differentiation. Contrary to other reports, not only was FNA alone more sensitive than CNB alone, the addition of CNB to an already negative FNA failed to increase sensitivity in the detection of carcinoma. However, CNB did contribute to a more definitive diagnosis in some cases. The authors also found FNA to be more cost effective than CNB for palpable breast lesions when time and effort are taken into consideration. This reinforces the benefit of FNA over CNB in the detection of early stage breast carcinoma. Cancer 1996;78:773-7.

Previous findings from a clinical trial (Protocol B-06) conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) indicated the worth of lumpectomy and breast irradiation for treating breast cancer. After the discovery by NSABP staff members of falsified information on patients enrolled in the study by St. Luc Hospital in Montreal, separate audits were conducted at St. Luc Hospital and other participating institutions. We report the results of both audits and update the study findings through an average of 12 years of follow-up.Patients with either negative or positive axillary nodes and tumors 4 cm or less in diameter were randomly assigned to one of three treatments: total mastectomy, lumpectomy followed by breast irradiation, or lumpectomy without irradiation. Three cohorts of patients were analyzed. The first cohort included all 2105 randomized patients, who were analyzed according to the intention-to-treat principle. The second cohort consisted of 1851 eligible patients in the first cohort with known nodal status who agreed to be followed and who accepted their assigned therapy (among those excluded were 6 patients from St. Luc Hospital who were declared ineligible because of falsified biopsy dates). The third cohort consisted of the patients in the second cohort minus the 322 eligible patients from St. Luc Hospital (total, 1529 patients).Regardless of the cohort, no significant differences were found in overall survival, disease-free survival, or survival free of disease at distant sites between the patients who underwent total mastectomy and those treated by lumpectomy alone or by lumpectomy plus breast irradiation. After 12 years of follow-up, the cumulative incidence of a recurrence of tumor in the ipsilateral breast was 35 percent in the group treated with lumpectomy alone and 10 percent in the group treated with lumpectomy and breast irradiation (P0.001).Our findings continue to indicate that lumpectomy followed by breast irradiation is appropriate therapy for women with either negative or positive axillary nodes and breast tumors 4 cm or less in diameter.

Background: For women undergoing breast conservative surgery or lumpectomy for early stage breast carcinoma, there are limited options for reconstruction. Options include the use of flap surgery and/or implants, and have a significant associated morbidity and cost. Autologous fat grafting is a new alternative that can achieve a good cosmetic result, while reducing patient morbidity and cost by avoiding more extensive surgery. Objective: The primary objectives are to assess patient satisfaction using the Breast-Q questionnaire and to evaluate fat graft volume. The secondary objectives are fat survival and assessment for complication (eg, fat necrosis, cysts), local recurrence, and the number of sessions needed for a satisfactory outcome. Methods: This study is a case series of 100 patients, at a single-center institute spanning one year. The inclusion criteria include: female sex, age 18 to 75, early state breast cancer (confirmed on ultrasound/ positron emission tomography-computed tomography and cytology), amenable to breast conservative surgery, and at least 6 months post-completion of radiotherapy/ hormone/chemotherapy. Exclusion criteria include patients with more advanced stages of breast cancer necessitating total mastectomy, those unsuitable for surgical excision, and those in whom lumpectomy is not feasible. The patients will have follow-up data collected at 6 months, 12 months and 5 years post-operatively. Results: This study will begin enrolment in January 2017. We anticipate that there will be good patient satisfaction with fat grafting. The risk for long-term breast cancer recurrence hasn’t been evaluated extensively in literature, however some clinical studies have shown no increased risk of breast cancer in appropriately selected patients at one year. Although some patients may develop complications from fat grafting (eg, necrosis/cysts) this should not confuse the radiological detection of breast cancer recurrence. Conclusions: Fat grafting is proving to be a viable option for reconstruction of lumpectomy defects with good patient satisfaction. The heterogeneous methods of reporting the harvesting of fat in literature may account for the variable outcomes described, and makes it difficult to compare results with similar studies. The long-term risk of breast cancer recurrence with fat grafting for lumpectomy defects is unknown. [JMIR Res Protoc 2016;5(3):e109]

Invasive ductal carcinoma is the most common histological pattern of breast cancer. Breast cancer metastasis has been observed at various sites but solitary metastasis to parotid gland is rare. Around 15 cases have been reported so far. We report a case of 61-year-old lady with early breast carcinoma metastasizing to ipsilateral parotid gland. She underwent breast conservation surgery with axillary dissection. Pathological stage was pT2(m) N0. Immunohistochemistry revealed hormone receptor positive, HER2-neu negative. She received adjuvant chemotherapy, radiotherapy, and hormonal therapy. Seven months later, she had parotid gland metastasis. She underwent superficial parotidectomy and right neck dissection. Hormonal therapy was changed to 2 nd line.

The present study was performed to evaluate the significance of biologic subtype and 21-gene recurrence score relative to local recurrence and local–regional recurrence after breast conservation treatment with radiation. Eastern Cooperative Oncology Group E2197 was a prospective randomized clinical trial that compared two adjuvant systemic chemotherapy regimens for patients with operable breast carcinoma with 1–3 positive lymph nodes or negative lymph nodes with tumor size >1.0 cm. The study population was a subset of 388 patients with known 21-gene recurrence score and treated with breast conservation surgery, systemic chemotherapy, and definitive radiation treatment. Median follow-up was 9.7 years (range = 3.7–11.6 years). The 10-year rates of local recurrence and local–regional recurrence were 5.4 % and 6.6 %, respectively. Neither biologic subtype nor 21-gene Recurrence Score was associated with local recurrence or local–regional recurrence on univariate or multivariate analyses (all P ≥ 0.12). The 10-year rates of local recurrence were 4.9 % for hormone receptor positive, HER2-negative tumors, 6.0 % for triple negative tumors, and 6.4 % for HER2-positive tumors (P = 0.76), and the 10-year rates of local–regional recurrence were 6.3, 6.9, and 7.2 %, respectively (P = 0.79). For hormone receptor positive tumors, the 10-year rates of local recurrence were 3.2, 2.9, and 10.1 % for low, intermediate, and high 21-gene recurrence score, respectively (P = 0.17), and the 10-year rates of local–regional recurrence were 3.8, 5.1, and 12.0 %, respectively (P = 0.12). For hormone receptor- positive tumors, the 21-gene recurrence score evaluated as a continuous variable was significant for local–regional recurrence (hazard ratio 2.66; P = 0.03). The 10-year rates of local recurrence and local–regional recurrence were reasonably low in all subsets of patients. Neither biologic subtype nor 21-gene recurrence score should preclude breast conservation treatment with radiation.

Purpose: To determine the accuracy of using the lumpectomy scar, specifically the midpoint or center of the scar, to define the tumor bed in the electron beam boost for the treatment of early stage breast carcinoma. Methods and Materials: Electron boost simulation films from 316 cases of early breast carcinoma treated with lumpectomy and radiotherapy were reviewed. For each case which had surgically placed lumpectomy bed clips ( N = 316), four clinical set-up methods ("hypothetical fields") of several field sizes were compared to the actual location of the tumor bed (as defined by the surgical clips). Each method was based on using the center of the scar as the center of the field and is described as follows: Method 1 uses a standard circular cone of a given diameter; method 2 also uses circular cones, but the diameter is based on the scar length; method 3 uses an oval field in which a constant margin is kept around the scar; method 4 results in an oblong field in which a 2 cm margin is placed on the lateral edge of the scar, but a larger margin around the center of the scar. The adequacy of each of these popular clinical set-up techniques was then analyzed for the population as a whole. "Inadequate" coverage was defined as any portion of the field edge coming within 1 cm of at least one surgical clip. Results: (1) Method 1: Inadequate coverage was found in 43%, 26%, and 17% of cases, using 7, 8, and 9 cm cones, respectively. (2) Method 2: Inadequate coverage was found in 88%, 61%, 36% and 20% of cases, with field size=scar length + 0, 2, 3, and 4 cm, respectively. (3) Method 3: Inadequate coverage was found in 34%, 17%, and 10% of cases, using 3, 3.5, and 4 cm margins, respectively. (4) Method 4: Inadequate coverage was found in 36% and 24% of cases using 3.5 and 4 cm margins around the scar center, respectively. Inadequate coverage was found in 51% and 42% of cases using margins equal to one-half the scar length or one-half the scar length + 1 cm, respectively. Conclusion: We conclude that the lumpectomy scar is often a poor indicator of the location of the underlying tumor bed as defined by surgical clips. We recommend the use of clip placement and simulation of the electron boost to maximize target definition.