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Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study is initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis and are scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: On June 30th 157 study sites from 15 countries are open for recruitment (Austria 2, Czech Republic 1, Finland 1, Germany 112, Greece 3, Italy 1, Norway 1, Poland 3, Portugal 5, Romania 2, Russia 1, Sweden 4, Switzerland 4, Spain 6, Turkey 11). 620 patients have been included in the study. Among patients who converted to ycN0 status, 144 have been scheduled for ALND, 157 for TAD and 49 for SLNB. The study is still open for further international study sites. Funding: AGO-B, Claudia-von Schilling Foundation, Ehmann Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Target accrual: 3000 patients worldwide Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michaelis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Rosa Di Micco, Dawid Murawa, David Pinto, Florentia Peintinger, Christine Solbach, Matilda Appelgren, Jens-Uwe Blohmer, Michael Weigel, Gabriele Kaltenecker, Michael Schrauder, Janine Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Alexander Sergeevich Emelyanov, Elisabeth Thiemann, Semra Gunay, Sybille Loibl, Maggie Banys-Paluchowski. AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-04.

Background Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of sentinel node biopsy alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NAC). However methods for TAD are still under investigation. Methods Magseed®, a non-radioactive magnetic marker was used to mark the biopsied positive TLN after NAC. The SLNB with the standard technetium-based method and the selective TLNB with Magseed® localization were performed in 40 patients. The TLNs were identified with the Sentimag® probe and excised in all patients. Specimen x-ray was performed to confirm the Magseed® within the prior to NAC biopsied and clipped lymph node. Results The TLN identification rate was 100% (40/40), the SLN identification rate was 82.5% (33/40), the concordance rate between the TLN and the SLN was 65% (26/40). Complications according Magseed® deployment or identification could not be observed. Conclusion Magseed® is a reliable and feasible marker for the identification of TLNs after NAC., Highlights • TLNB is an accurate method for the identification of marked lymph nodes after NAC. • Selective excision of TLNs is feasible. • Magseed® allows a non-radioactive, wireless marking of TLNs.

Cancers 13(7), 1565 (2021). doi:10.3390/cancers13071565 special issue: "Special Issue "Clinical Trials in Breast Cancer" / Special Issue Editor: Prof. Dr. Gilles Freyer, Guest Editor", Published by MDPI, Basel

Background: Mammography screening programs in Europe revealed a 25–30% breast cancer mortality reduction in women between 50 and 74 years. Early cancer detection and less radical treatment in dedicated multidisciplinary breast centers have improved breast cancer care. Breast population-based screening (persons are individually identified and personally invited to attend screening) is intended to detect breast cancer at an early stage to enable lower mortality rates. Methods: The status of implementation of cancer screening programs among European countries, quality parameters and possible differences will be reviewed. Results: Implementation of the recommended maximum age range was adopted in most programs. Almost all the European countries established digital mammography as the method of screening instead of screen-film mammography. Inequalities in implementation of cancer screening in the European Union have been observed. Conclusion: Improvement of data quality and mortality registries linked to the screening programs are needed.

Axillary surgery has undergone considerable changes in recent years, especially in relation to patients who undergo neoadjuvant chemotherapy (NACT). Due to constantly decreasing rates of recurrence and death from breast cancer, modern surgical strategies aim at de-escalating the extent of local treatment and avoiding unnecessary procedures. This relates especially to lymph node surgery which is associated with considerable morbidity. In patients who initially present with clinically node-negative disease, sentinel lymph node biopsy (SLNB) is increasingly performed after NACT. The determination of the post-NACT nodal status does not only spare patients from additional surgery but also allows the assessment of pathologic complete response which is increasingly becoming an important tool for treatment planning. Since more than 70% of these patients have a ypN0 status after NACT, future trials will aim to identify patients who might be spared any axillary surgery after NACT. In patients who initially present with positive lymph nodes, the success rates of SLNB in terms of detection and accuracy are less favorable compared to those in patients who undergo primary surgery. The clinical significance of this is unclear. To reduce unnecessary axillary dissection in patients with cN1ycN0 status, prospective outcome data after SLNB without further lymph node removal are urgently needed. Improvements in surgical technique by localizing positive nodes at the time of diagnosis and removing them in a targeted surgical procedure (targeted axillary dissection) are under evaluation. Risk assessment and patient selection (including gene expression profiles) might be other ways of safely omitting axillary dissection.

Background Prepectoral implant placement is an innovative option for breast reconstruction, due to multiple advantages over subpectoral implant placement. The adoption of various ADMs and meshes supports the utilization of the prepectoral technique. Methods 200 breasts were reconstructed with prepectoral implant placement after nipple-sparing mastectomy in a one-stage direct-to-implant procedure. The implants were completely covered and fixed with porcine ADMs (Strattice™ or Artia™), or with synthetic meshes (TIGR®). The pectoralis major muscle was not detached at all and kept intact entirely. Results Minor complications included minimal nipple necrosis without further intervention and complete healing in 14 breasts (7.0%). Major complications comprised implant loss due to skin necrosis and wound infection in 7 breasts (3.5%), and hematoma with revision surgery in 8 breasts (4.0%). At a mean follow-up of 36 months cosmetic results were excellent and good in 180 breasts (90.0%), sufficient in 13 breasts (6.5%) and insufficient in 7 breasts (3.5%). Breast animation deformity and implant displacement could not be observed, while implant rotation was documented in 5 breasts (2.5%). Capsular contractures grade III or IV could not be observed neither in patients with previous radiotherapy nor in patients with radiotherapy to the reconstructed breast. Conclusions The single-stage direct-to-implant prepectoral implant placement after NSM with complete coverage of the implant with ADM or synthetic mesh represents a novel and feasible technique for breast reconstruction. This technique provides an alternative to the subpectoral implant placement with excellent cosmetic results avoiding the disadvantages of the subpectoral implant placement.

Clinical observations about lack of survival benefit after extensive axillary surgery and biological discordance between primary breast tumors and axillary lymph nodes raise the question of the actual metastatic potential of axillary nodal disease. The exploration of intratumoral heterogeneity and detection of genomic differences between the primary and lymph nodes indicate some similarity between the number of mutations in synchronous axillary node metastases and those in the primary lesion, suggesting a favorable prognosis. The hematogenous route of metastasis needs to be considered in findings of different subclones between nodal and distant metastases. Modern tools such as whole-genome sequencing applied in multiple tumor areas may guide more precisely the extent of axillary surgery. (C) 2018 S. Karger GmbH, Freiburg

Bone is the most common site of distant metastases in breast cancer that can cause severe and debilitating skeletal related events (SRE) including hypercalcemia of malignancy, pathologic fracture, spinal cord compression and the need for palliative radiation therapy or surgery to the bone. SRE are associated with substantial pain and morbidity leading to frequent hospitalization, impaired quality of life and poor prognosis. The past 25 years of research on the pathophysiology of bone metastases led to the development of highly effective treatment options to delay or prevent osseous metastases and SRE. Management of bone metastases has become an integral part of cancer treatment requiring expertise of multidisciplinary teams of medical and radiation oncologists, surgeons and radiologists in order to find an optimal treatment for each individual patient. A group of international breast cancer experts attended a Skeletal Care Academy Meeting in November 2012 in Istanbul and discussed current preventive measures and treatment options of SRE, which are summarized in this evidence-based consensus for qualified decision-making in clinical practice. (C) 2014 Elsevier Ltd. All rights reserved.

PURPOSE OF REVIEW In this article, recent developments with molecular profiling in breast cancer and future directions will be highlighted. RECENT FINDINGS Gene-expression profiling revealed four major biologic subtypes that reflect intertumoral heterogeneity of breast cancer and have led to the development of prognostic tools to facilitate adequate treatment in early breast cancer. A number of commercially available prognostic tests have been introduced for implementation in clinical routine. Also, predictive tools and approaches to characterize molecular portraits of metastatic breast cancer in order to overcome treatment resistance have been investigated. Efforts to identify the quantity and quality of clonal selection and genomic variability through modern genomic profiling led successfully to new insights into targeted treatment with more effective drugs and the promise to overcome resistance. SUMMARY Multigene approaches and novel microarray platforms such as the next-generation sequencing technology are feasible in clinical practice in order to assess the prognosis more precisely and to identify new molecular targets for developing more effective drugs in the near future.

The German, Austrian and Swiss (D.A.CH) Societies of Senology gathered together in 2012 to address dwelling questions regarding axillary clearance in breast cancer patients. The Consensus Panel consisted of 14 members of these societies and included surgical oncologists, gynaecologists, pathologists and radiotherapists. With regard to omitting axillary lymph node dissection in sentinel lymph node macrometastases, the Panel consensually accepted this option for low-risk patients only. A simple majority voted against extending radiotherapy to the axilla after omitting axillary dissection in N1 disease. Consensus was yielded for the use of axillary ultrasound and prospective registers for such patients in the course of follow-up. The questions regarding neoadjuvant therapy and the timing of sentinel lymph node biopsy failed to yield consensus, yet both options (before or after) are possible in clinically node-negative disease.

Background Surgical and systemic treatment modalities for breast cancer (BC) patients with micrometastatic disease in the sentinel lymph node biopsy (SNB) are controversial. The aim of this study was to evaluate decisional factors associated with assignment of adjuvant chemotherapy (CT). Patients and Methods In a retrospective multicentric European study we evaluated cases of primary BC patients who underwent SNB. Logistic regression (LR) and recursive partitioning analyses (RPA) were performed to determine factors associated with CT. Results Of the 172 patients with micrometastatic disease, 39.5% received adjuvant CT. In the group treated with CT, patients tended to be younger (P = 0.001), with higher grade (P = 0.001) and HER2 positive tumors (P = 0.006) compared to patients without CT. In multivariate LR, age (P = 0.0027), high grading (P = 0.01) HER2 positivity (P = 0.03), and positive non-SN status (P = 0.03) were significantly associated with CT. RPA demonstrated that tumor grade, and not the non-SN status, was the first split in the partition tree followed by HER2 status, and non-SN status influencing the probability for CT administration. Conclusion High tumor grade is the main decisional factor followed by HER2 positivity and then by the positive non-SN status for CT in micrometastatic disease in the SN. J. Surg. Oncol. 2012; 106:703–707. © 2012 Wiley Periodicals, Inc.

Purpose To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) –positive breast cancer. Methods We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence–free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. Results Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor–positive tumors. Conclusion Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

// Sarah Kammerer 1, 2 , Armin Sokolowski 1, 9 , Hubert Hackl 3 , Dieter Platzer 1 , Stephan Wenzel Jahn 4 , Amin El-Heliebi 5 , Daniela Schwarzenbacher 6 , Verena Stiegelbauer 6 , Martin Pichler 6, 7 , Simin Rezania 1, 2 , Heidelinde Fiegl 8 , Florentia Peintinger 4 , Peter Regitnig 4 , Gerald Hoefler 4 , Wolfgang Schreibmayer 1, 2 , Thomas Bauernhofer 2, 6 1 Molecular Physiology Group, Institute of Biophysics, Medical University of Graz, Austria 2 Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Austria 3 Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Austria 4 Institute of Pathology, Medical University of Graz, Austria 5 Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Austria 6 Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria 7 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 8 Department of Gynecology and Obstetrics, Medical University of Innsbruck, Austria 9 Present address: Division of Prosthodontics, Restorative Dentistry, Periodontology and Implantology, Medical University of Graz, Austria Correspondence to: Thomas Bauernhofer, email: thomas.bauernhofer@medunigraz.at Keywords: KCNJ3, GIRK1, biomarker, estrogen receptor positive breast cancer, RNA in situ hybridization Received: June 04, 2016 Accepted: October 26, 2016 Published: November 08, 2016 ABSTRACT Numerous studies showed abnormal expression of ion channels in different cancer types. Amongst these, the potassium channel gene KCNJ3 (encoding for GIRK1 proteins) has been reported to be upregulated in tumors of patients with breast cancer and to correlate with positive lymph node status. We aimed to study KCNJ3 levels in different breast cancer subtypes using gene expression data from the TCGA, to validate our findings using RNA in situ hybridization in a validation cohort (GEO ID GSE17705), and to study the prognostic value of KCNJ3 using survival analysis. In a total of > 1000 breast cancer patients of two independent data sets we showed a) that KCNJ3 expression is upregulated in tumor tissue compared to corresponding normal tissue ( p < 0.001), b) that KCNJ3 expression is associated with estrogen receptor (ER) positive tumors ( p < 0.001), but that KCNJ3 expression is variable within this group, and c) that ER positive patients with high KCNJ3 levels have worse overall ( p < 0.05) and disease free survival probabilities ( p < 0.01), whereby KCNJ3 is an independent prognostic factor ( p

Background Neoadjuvant chemotherapy for breast cancer reduces tumour cellularity, the percentage of the primary tumour area that is composed of invasive tumour cells. Minimal residual tumour cellularity (5 per cent or less of tumour area composed of invasive tumour cells) may be associated with an increased risk of false-negative intraoperative margins. The aim of this study was to evaluate the incidence of minimal residual tumour cellularity after neoadjuvant chemotherapy and its impact on the frequency of false-negative margins and conversion from breast-conserving surgery to mastectomy. Methods The final pathology slides of 510 patients who had surgery after neoadjuvant chemotherapy were reviewed. Results Of 396 patients with residual invasive breast cancer after neoadjuvant chemotherapy, 100 specimens (25·3 per cent) had minimal residual cellularity; this was more frequent in patients with invasive lobular carcinoma (17·0 versus 5·1 per cent; P < 0·001) or well and moderately differentiated carcinoma (68·0 versus 52·4 per cent; P = 0·007). Among 149 patients who had initial breast-conserving surgery, false-negative intraoperative margin rates were 23 per cent in specimens with minimal and 13·8 per cent in those with higher residual cellularity (P = 0·210). There was no significant difference in the rate of conversion to mastectomy between the groups. Conclusion Minimal residual cellularity after neoadjuvant chemotherapy occurred in about 25 per cent of specimens, but did not alter the rate of false-negative intraoperative margins.

The standard treatment for early breast cancer comprises wide local excision, sentinel lymph node biopsy or axillary lymph node dissection, adjuvant medical treatment and radiotherapy to the whole breast. Many studies suggest that local control plays a crucial role in overall survival. The local recurrence rate is estimated to be 1% per year and varies between 4 and 7% after 5 years and up to 10 to 20% in the long-term follow up. On the basis of low local recurrence rates the concept of whole breast irradiation comes up for discussion, and partial breast irradiation (PBI) is increasingly under consideration. Intraoperative radiotherapy (IORT) is referred to as the delivery of a single high dose of irradiation directly to the tumor bed (confined target) during surgery. PBI (limited field radiation therapy, accelerated partial breast irradiation APBI) is the irradiation exclusively confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery without whole breast irradiation. Various methods and techniques for IORT or PBI are under investigation. The advantage of a very short radiation time or the integration of the complete radiation treatment into the surgical procedure convinces at a first glance. The promising short-term results of those studies must not fail to mention that local recurrence rates could probably increase and furthermore give rise to distant metastases and a reduction in overall survival. The combination of IORT in boost modality and whole breast irradiation has the ability to reduce local recurrence rates. The EBCTCG overview approves that differences in local treatment that substantially affect local recurrence rates would avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Purpose: We examined whether the response predicted by a 30-gene pharmacogenomic test correlated with the residual cancer burden (RCB) after preoperative chemotherapy with paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC). Experimental Design: Gene expression profiling was done at diagnosis in 74 patients with stages I to III breast cancer and was used to calculate a pharmacogenomic score and predict response to chemotherapy [pathologic complete response (pCR) or residual disease (RD)]. All patients received 6 months of preoperative T/FAC. Following pathologic review, a RCB score was calculated based on residual tumor and lymph node features. Four RCB classes were assigned; RCB-0 (pCR), RCB-I (near-PCR), RCB-II (moderate RD), and RCB-III (extensive RD). The correlations between the pharmacogenomic score, predicted pathologic response, RCB score, and RCB class were examined. Results: Thirty-three patients were predicted to have pCR, and 40 were predicted to have RD. Observed responses were RCB-0: n = 20 (27%); RCB-I: n = 5 (7%); RCB-II: n = 36 (49%); and RCB-III: n = 13 (16%) patients. Pharmacogenomic and RCB scores were correlated (Pearson's R = −0.501, P < 0.0001). There was no difference between the mean genomic predictor scores for RCB-0/I groups (P = 0.94), but these were different from the mean scores of the RCB-II/III groups (P < 0.001). Among the 25 patients with RCB-0/I response, 19 (76%) were predicted to achieve pCR. The pharmacogenomic test correctly predicted RD in 92% of the patients with RCB-III, which corresponds to chemotherapy-resistant disease. Conclusions: The 30-gene pharmacogenomic test showed good correlation with the extent of residual invasive cancer burden measured as both continuous and categorical variables.

BACKGROUND. A previously published prospective randomized phase 3 trial showed that administration of 24 weeks of primary systemic chemotherapy (PST) with paclitaxel and FEC75 (fluorouracil, epirubicin, cyclophosphamide) concurrently with trastuzumab in patients with HER2-positive primary breast cancer resulted in a 60% pathologic complete response rate (PCR) with no associated severe cardiac toxicity. The purpose of this study was to review the efficacy and safety of a similar regimen outside the setting of a clinical trial. METHODS. Patients with HER2-positive breast cancer (defined as either immunohistochemical 3+ or fluorescence in situ hybridization-positive) that had received 24 weeks of neoadjuvant trastuzumab concurrently with taxane and anthracycline-based chemotherapy between 2004 and 2006 were included in the analysis. PST chemotherapy consisted of paclitaxel (80 mg/m2) weekly for 12 weeks followed by 4 cycles of FEC75 (500 mg/m2, 75 mg/m2, and 500 mg/m2, respectively). RESULTS. Forty patients were identified. The median age was 48 years (range, 29–81). In all, 60% of patients had stage III disease and 4 had inflammatory breast cancer. The PCR rate was 55% (95% confidence interval [CI], 38.5%–70.7%). At a median follow-up of 19 months. 5 patients had a recurrence, of which 4 did not achieve a PCR. No severe cardiac events were observed. CONCLUSIONS. Stage II and III HER2-positive breast cancer patients achieved a high rate of PCR with trastuzumab given concurrently with paclitaxel and FEC75 chemotherapy. No severe cardiac events were observed with the regimen. The data concur with the results of a previously published trial. Cancer 2007. © 2007 American Cancer Society.

Residual tumor size after neoadjuvant chemotherapy is an important consideration in surgical planning. We examined the accuracy of the combination of mammography and sonography in predicting pathologic residual tumor size. Tumor size was evaluated by physical examination, mammography, and sonography at diagnosis and before surgery in 162 breast cancer patients who received neoadjuvant chemotherapy. Agreement between the predicted and the pathologic responses and the predicted and the pathologic tumor sizes was calculated. The effect of invasive lobular carcinoma, high nuclear grade, hormone receptor positivity, and the presence of an extensive intraductal component on the accuracy of mammography and sonography in predicting pathologic residual tumor size was analyzed. Forty-two patients (25.9%) had a pathologic complete response (pCR). Overall agreement between predicted and pathologic responses was 53% for physical examination, 67% for mammography plus sonography, and 63% for physical examination plus mammography and sonography. The sensitivity of mammography and sonography in predicting pCR was 78.6%, and the specificity was 92.5%; the accuracy was 88.9%. Residual tumor size determined by mammography and sonography correlated with pathologic residual tumor size (r = .662); pathologic tumor size was within .5 cm of predicted in 69.1% of patients. Multivariate analysis showed that pathologic residual tumor size was underestimated for lobular carcinoma and overestimated for poorly differentiated tumors. The combination of mammography and sonography has a high accuracy in predicting pCR after neoadjuvant chemotherapy. Agreement of residual tumor size in mammography and sonography with pathologic residual tumor size was moderate.

The use of preoperative chemotherapy for breast cancer is becoming a widely accepted treatment option. Survival of breast cancer patients treated with preoperative chemotherapy has been shown to be equivalent to that of breast cancer patients treated with postoperative chemotherapy.1,2 However, preoperative therapy has advantages: it permits in vivo assessment of tumor response to chemotherapy and increases rates of breast-conserving therapy (BCT) without significantly increasing the risk of local recurrence.2 Although preoperative chemotherapy has been shown to increase the proportion of patients who are able to undergo BCT,1,3–5 several critical questions regarding this approach have not been resolved. First, it is not known whether preoperative chemotherapy versus the more common approach of postoperative chemotherapy has an effect on the volume of breast tissue resected. Until now, it has been assumed that if preoperative chemotherapy increases the proportion of patients able to undergo segmental resection rather than mastectomy, patients who receive preoperative chemotherapy will have less breast tissue excised compared with patients with the same tumor size at presentation who receive postoperative chemotherapy. However, in theory, the actual volume of tissue resected could be no different or even larger because surgeons remove a large amount of tissue in an attempt to obtain clear margins. To our knowledge, how preoperative versus postoperative chemotherapy affects the volume of tissue excised has not been formally studied. The volume of breast tissue resected in patients undergoing BCT is known to have a direct impact on cosmesis.6 Second, it has not been determined whether preoperative chemotherapy increases the number of operative procedures required to achieve negative margins. Since chemotherapy shrinks tumors in different ways and rarely concentrically, does the use of preoperative chemotherapy make obtaining clear margins more difficult and therefore result in more surgical procedures required for margin control? We performed this study to determine the effect of preoperative versus postoperative chemotherapy on the volume of tissue excised and the number of breast operations in patients undergoing surgery for breast cancer. This type of information is critically important to patients when they are considering their surgical options and the risks and potential benefits of various approaches to treatment.

We conducted a prospective randomized study to compare the results of 3 cycles of epidoxorubicin/docetaxel to 6 cycles of epidoxorubicin/docetaxel prior to surgery in breast cancer patients with clinical stages II and III. Forty-five patients eligible for neoadjuvant chemotherapy were randomly assigned to receive either 3 (group 1) or 6 (group 2) cycles of epidoxorubicin/docetaxel prior to surgery. Chemotherapy consisted of epidoxorubicin 75 mg/m and docetaxel 75 mg/m on day 1 in 3-week cycles. The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the rates of breast-conserving surgery and the axillary lymph node status in both groups. A pCR occurred in 10% (two of 20) in Group 1 and in 36% (nine of 25) in Group 2, which was statistically significant (p=0.045). Breast-conserving surgery could be performed in 70% (14 of 20) in Group 1 and in 76% (19 of 25) in Group 2 (p=0.065). Axillary lymph node status was negative in 45% (nine of 20) in Group 1 and 52% (13 of 25) in Group 2 (p=0.86). We conclude that 6 cycles of pre-operative epidoxorubicin/docetaxel versus 3 cycles of pre-operative epidoxorubicin/docetaxel significantly increases the pCR rates for breast cancer patients.

The aim of this study is to evaluate the rate of axillary recurrences in sentinel lymph node (SLN)-negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). Between May 1999 and February 2002, 333 consecutive patients with primary invasive breast cancer up to 4 cm and clinically negative axillae were entered into this prospective study. Sentinel lymph nodes were identified using the combined method with blue dye (Patent blue V) and technetium 99m-labelled albumin (Nanocoll). Sentinel lymph nodes were examined by frozen sections, standard haematoxylin and eosin staining and immunohistochemistry staining. In SLN-positive patients, ALND was performed. Sentinel lymph node-negative patients had no further ALND. The SLN identification rate was 98.5% (328 out of 333). In all, 128 out of 328 (39.0%) patients had positive SLNs and complete ALND. A total of 200 out of 328 (61.0%) patients were SLN negative and had no further ALND. The mean tumour size of SLN-negative patients was 16.5 mm. The mean number of SLNs removed was 2.1 per patient. There were no local or axillary recurrences at a median follow-up of 36 months. The absence of axillary recurrences after SLNB without ALND in SLN-negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity than ALND. Short-term results are very promising that SLNB without ALND in SLN-negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumours.

To evaluate the role of adjuvant radiotherapy for an unexpected malignancy of the breast, known as phyllodes tumor, a retrospective study was undertaken. Between 1994 and 2002, six female patients with a phyllodes tumor (borderline, n = 2; malignant, n = 4) were irradiated after modified radical mastectomy at our institution. No patient received adjuvant systemic therapy. Two patients experienced local failure, after 17 months (malignant) and 23 (borderline) months of observation. One of the patients with local relapse died intercurrently, the other because of multiple pulmonary metastases. Four patients are alive and show no evidence of disease. Median follow-up was 33.8 months (range 29–42 months). Based on the data from the literature and the authors’ findings, it is concluded that surgery with wide negative margins is the preferred initial treatment option. There is no indication for axillary dissection, since these tumors rarely metastasize to regional lymph nodes. In patients with phyllodes tumors showing adverse prognostic factors, postoperative irradiation is recommended.

There has been little information regarding lymph node-positive breast cancer patients with extracapsular extension (ECE). The aim of this study was to evaluate the role of ECE in predicting survival and relapse rates. From 1994–2002, 1,078 lymph node-positive women with breast carcinoma were treated at our institution, whereas 301 patients (27.9%) presented with ECE. 91 patients (30.2%) were identified as having three or less lymph nodes involved, 27.9% patients four to six, 15.6% patients seven to nine, and 26.2% patients ten or more nodes, respectively. The median age was 58.4 years (range: 28–84 years) and the median follow-up 34 months (range: 2–99 months). Nodal irradiation was given to patients with four or more positive lymph nodes. Chemotherapy was administered to 69.8%, hormonal therapy to 53.2%, and combined systemic treatment to 26% of patients. The 1-, 3-, and 5-year overall survival (OS) was 98%, 84%, and 73%, the 1-, 3-, and 5-year disease-free survival (DFS) 95%, 69%, and 58%, and the 1-, 3-, and 5-year metastasis-free survival (MFS) 96%, 73%, and 60%. The relapse rates were 6.6% (local), 0.3% (supraclavicular), 0.7% (isolated axillary), 1% (local + axillary), and 0.7% (local + supraclavicular), respectively. 81 patients (27%) developed distant metastases. In December 2002, 245 patients (81.4%) were alive, 202/245 without progression, 32/245 with distant metastases, 5/245 with local/locoregional recurrence, and 6/245 patients with local and distant failure. Isolated axillary nodal failure remains low in lymph node-positive patients with ECE. Balancing the risks and benefits of irradiation, we continue to recommend that complete axillary irradiation is not routinely indicated after adequate axillary dissection.

Background and Objectives Sentinel lymph node biopsy (SLNB) is an accurate method for axillary staging in patients with early breast cancer. The aim of this study was to evaluate the accuracy and the feasibility of SLNB in breast cancer patients who had received preoperative (neoadjuvant) chemotherapy. Methods Patients with advanced breast cancer stage II or III who were treated with neoadjuvant chemotherapy were included in the study. Sentinel lymph node (SLN) identification and biopsy was attempted and performed, and axillary lymph node dissection (ALND) was performed in the same surgical procedure after SLNB. The histopathologic examination of the SLNs and the dissected axillary lymph nodes was performed and nodal status was compared. Results Thirty patients were included in the study. After peritumoural injection of technetium-99m labelled human albumin and subareolar subcutaneous injection of blue dye, the SLNs could be identified in 26/30 patients (identification rate 86.7%). In 4/30 patients (13.3%) SLNs could not be identified. In 25/26 patients (96.2%) SLNs accurately predicted the axillary status. Eleven patients had negative SLNs and negative nodes in ALND. Six patients had positive SLNs and positive nodes in ALND. In eight patients SLNs only were positive and nodes in ALND were negative. One patient had a false-negative SLNB, calculating a false-negative rate of 6.7% (1/15). Conclusions SLNB is a well introduced technique for axillary staging in patients with early breast cancer. The accuracy of SLNB after neoadjuvant chemotherapy is similar to patients with primary surgery. SLNB could be an alternative to ALND in a subgroup of patients after neoadjuvant chemotherapy, and therefore could reduce morbidity due to surgery in those patients. Due to small numbers of patients, further evaluation in this subset of patients is required. J. Surg. Oncol. 2003;84:63–67. © 2003 Wiley-Liss, Inc.

Einleitung: Seit der Einführung der Sentinellymphknotenbiopsie (SLNB) zum axillären Staging bei Mammakarzinompatientinnen hat sich diese Operationstechnik in den meisten Brustzentren etabliert. Die Idee, mit einem weniger invasiven Eingriff als der axillären Dissektion den Nodalstatus exakt zu evaluieren, ist faszinierend und entspricht dem Gesamtkonzept in der Behandlung des Mammakarzinoms, den operativen Eingriff so wenig invasiv wie möglich zu gestalten. An wenigen Abteilungen wurde bereits dazu übergegangen, bei negativem Sentinellymphknoten (SLN) auf die Axilladissektion zu verzichten. Patientinnen und Methode: Von März 1998 bis März 2002 wurde an unserer Abteilung an 500 Patientinnen mit invasivem Mammakarzinom die Technik der SLNB angewandt. Anfangs wurde die Axilladissektion direkt im Anschluss an die SLNB durchgeführt. Nach der Lernphase an 75 Patientinnen mit einer Sensitivität von 96,2% und einer falsch negativen Rate von 3,8%, wurde bei Patientinnen mit negativem SLN unter definierten Voraussetzungen auf eine Axilladissektion verzichtet. Zusätzlich wurde aber das Spektrum erweitert und die Methode bei Patientinnen mit multizentrischem Karzinom und bei Patientinnen nach neoadjuvanter Chemotherapie evaluiert. Zur Auffindung des SLN wurde die kombinierte Methode mit blauem Farbstoff und mit Technetium 99m markiertem Humanalbumin verwendet. Ergebnisse: 500 SLNB wurden durchgeführt. Die Detektionsrate für das gesamte Kollektiv betrug 86,2%. Nach Bereinigung der Patientinnen mit multizentrischem Karzinom und der Patientinnen nach neoadjuvanter Chemotherapie betrug die Detektionsrate 94,5%. Insgesamt war der SLN in 41,3% der Patientinnen positiv, in 58,7% der Patientinnen negativ. Diskussion: Die SLNB ist eine probate Alternative zur Axilladissektion bei Patientinnen mit Mammakarzinom unter definierten Voraussetzungen.

Neoadjuvant systemic therapy is being used increasingly in the treatment of early-stage breast cancer. Response, in the form of pathological complete response, is a validated and evaluable surrogate end point of survival after neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, there is a current lack of uniformity in the definition of pathological complete response. A review of standard operating procedures used by 28 major neoadjuvant breast cancer trials and/or 25 sites involved in such trials identified marked variability in specimen handling and histologic reporting. An international working group was convened to develop practical recommendations for the pathologic assessment of residual disease in neoadjuvant clinical trials of breast cancer and information expected from pathology reports. Systematic sampling of areas identified by informed mapping of the specimen and close correlation with radiological findings is preferable to overly exhaustive sampling, and permits taking tissue samples for translational research. Controversial areas are discussed, including measurement of lesion size, reporting of lymphovascular space invasion and the presence of isolated tumor cells in lymph nodes after neoadjuvant therapy, and retesting of markers after treatment. If there has been a pathological complete response, this must be clearly stated, and the presence/absence of residual ductal carcinoma in situ must be described. When there is residual invasive carcinoma, a comment must be made as to the presence/absence of chemotherapy effect in the breast and lymph nodes. The Residual Cancer Burden is the preferred method for quantifying residual disease in neoadjuvant clinical trials in breast cancer; other methods can be included per trial protocols and regional preference. Posttreatment tumor staging using the Tumor-Node-Metastasis system should be included. These recommendations for standardized pathological evaluation and reporting of neoadjuvant breast cancer specimens should improve prognostication for individual patients and allow comparison of treatment outcomes within and across clinical trials.

Conventional radiotherapy after breast-conserving therapy is confined to 50-55 Gy external beam radiation therapy (EBRT) to the whole breast and 10-16 Gy external boost radiation to the tumour bed or brachytherapy to the tumour bed. Local recurrence rate after breast-conserving surgery varies between 5 and 18%. External boost radiation can partially miss the tumour bed and therefore can result in local failure. Intra-operative radiotherapy (IORT) as a high precision boost can prevent a 'geographical miss'. From October 1998 to December 2000, 156 patients with stage I and stage II breast cancer were operated upon in a dedicated IORT facility. After local excision of the tumour, the tumour bed was temporarily approximated by sutures to bring the tissue in the radiation planning target volume. A single dose of 9 Gy was applied to the 90% reference isodose with energies ranging from 4 to 15 MeV, using round applicator tubes 4-8 cm in diameter. After wound healing, the patients received additional 51-56 Gy EBRT to the whole breast. No acute complications associated with IORT were observed. In 5 patients, a secondary mastectomy had to be performed because of tumour multicentricity in the final pathological report or excessive intraductal component. 2 patients developed rib necroses. In 7 patients, wound healing problems occurred. After a mean follow-up of 18 months, no local recurrences were observed. Cosmesis of the breast was very good and comparable to patients without IORT. Preliminary data suggest that IORT given as a boost after breast-conserving surgery could be a reliable alternative to conventional postoperative fractionated boost radiation by accurate dose delivery and avoiding geographical misses, by enabling smaller treatment volumes and complete skin-sparing and by reducing postoperative radiation time by 7-14 days.

The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-Pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports of 100 cases from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists. The size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis, and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-Pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among pathologists was 0.931 (95% confidence interval (CI) 0.908-0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% CI 0.539-0.626). The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient=0.980; 95% CI 0.954-0.992), than the primary component (overall concordance correlation coefficient=0.795; 95% CI 0.716-0.853). At a median follow-up of 12 years residual cancer burden determined by each of the pathologists had the same prognostic accuracy for distant recurrence-free and survival (overall concordance correlation coefficient=0.995; 95% CI 0.989-0.998). Residual cancer burden assessment is highly reproducible, with reproducible long-term prognostic significance.

UNLABELLED Acellular dermal matrices (ADM) have been used frequently in therapeutic and prophylactic breast procedures. To date there have been no reports on vascularisation of ADMs and formation of tissue around them as seen with modern non-invasive imaging techniques such as contrast-enhanced ultrasound (CEUS). In this case series, we used CEUS to investigate the features of ADM in relation to vascular ingrowth and scaffold for "new" tissue formation. This is a retrospective evaluation of patients who underwent successful skin- and nipple-sparing mastectomy (SSM, NSM) with immediate IBBR using ADM from May 31, 2010, through December 28, 2012. Over a 24-month period, 16 patients, with an average age of 44 years (range 27-70 years), were evaluated with CEUS. No contrast agent allergies or side effects were reported for the ultrasound examination. After contrast agent injection (1-18 months postoperatively), homogeneous normal enhancement in the ADM and peripheral region with physiological tissue formation was seen in all patients. In this small study, the most obvious contribution of CEUS is the in vivo evaluation of vascular ingrowth and tissue formation after IBBR with ADM after follow-up of 1-18 months postoperatively. LEVEL OF EVIDENCE III Retrospective cohort or comparative study; case-control study; or systematic review of these studies.

To evaluate retrospectively rates of local (LCR) and locoregional tumor control (LRCR) in patients with locally advanced breast cancer (LABC) who were treated with preoperative chemotherapy (primary systemic treatment, PST) followed by breast-conserving surgery (BCS) and either intraoperative radiotherapy with electrons (IOERT) preceding whole-breast irradiation (WBI) (Group 1) or with WBI followed by an external tumor bed boost (electrons or photons) instead of IOERT (Group 2). From 2002 to 2007, 83 patients with clinical Stage II or III breast cancer were enrolled in Group 1 and 26 in Group 2. All patients received PST followed by BCS and axillary lymph node dissection. IOERT boosts were applied by single doses of 9 Gy (90% reference isodose) versus external boosts of 12 Gy (median dose range, 6-16) in 2 Gy/fraction (ICRU). WBI in both groups was performed up to total doses of 51-57 Gy (1.7-1.8 Gy/fraction). The respective median follow-up times for Groups 1 and 2 amount 59 months (range, 3-115) and 67.5 months (range, 13-120). Corresponding 6-year rates for LCR, LRCR, metastasis-free survival, disease-specific survival and overall survival were 98.5, 97.2, 84.7, 89.2 and 86.4% for Group 1 and 88.1, 88.1, 74, 92 and 92% for Group 2, respectively, without any statistical significances. IOERT as boost modality during BCS in LABC after PST shows a trend to be superior in terms of LCR and LRCR in comparison with conventional boosts.

Aims: To evaluate the rate of axillary recurrences in sentinel lymph node (SLN) negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). Methods: Between May 1999 and February 2001 all patients who had primary invasive breast cancer and were SLN negative were eligible for this prospective study. SLNB was performed by using the combined method with radioactive tracer and blue dye. SLNs were examined by frozen section, standard H/E staining and immunohistochemistry staining. SLN negative patients did not receive further ALND. Follow-up was done three-monthly with clinical controls, blood samples and ultrasound of the breast and axilla. An annual mammogram was performed. Results: 116 patients with T1 or T2 invasive breast cancer were included in this trial. All 116 patients had negative SLNs in frozen sections, in H/E staining and in immunohistochemistry staining. The mean number of removed SLNs was 2.03±1.22. Mean tumor size was 17.15±7.62 mm. Postmenopausal patients totalled 79.3 and 20.7% of patients were premenopausal. No local or axillary recurrences occurred at a mean duration of follow-up of 22.12±6.38 months. Conclusion: The absence of axillary recurrences after SLNB without ALND in SLN negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity. Short term results are very promising. SLNB without ALND in SLN negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumors.

Fragestellung: Die skin-sparing Mastektomie wird nicht nur als therapeutische Option beim Mammakarzinom sondern auch zunehmend als eine prophylaktische operative Masnahme bei Mutationstragerinnen eingesetzt. Wir berichten von 28 Fallen, die nach der skin-sparing Mastektomie eine Brustrekonstruktion mittels Implantat und porciner Gewebematrix Strattice® erhielten. Methodik: 36 Brustrekonstruktionen wurden an 28 Patientinnen zwischen 26 und 71 Jahren durchgefuhrt. 7 Patientinnen hatten eine prophylaktische und 21 Patientinnen hatten eine therapeutische skin-sparing Mastektomie kombiniert mit einer Sentinel Lymphknotenbiopsie und/oder axillarer Dissektion. Nach der Mastektomie wurde das Implantat in eine subpektorale Tasche positioniert und der inferiore Teil des Implantates wurde mit der Gewebematrix Strattice® bedeckt und mit Nahten am M. Pectoralis und an der Submammarfalte fixiert. Alle Patientinnen erhielten eine antibiotische Prophylaxe und Drainagen, die je nach Fordermenge bis zu 2 Wochen belassen wurden. Ergebnisse: In einer Beobachtungszeit von 12 Monaten wurde in 5,6% (2/36) eine Wundheilungsstorung mit konsekutiver Entfernung des Implantates, in 5,6% (2/36) eine sekundare Nachblutung mit Revision und in 2,8% (1/36) der Falle eine Wundinfektion mit nachfolgender Antibiotikatherapie beobachtet. Hohe Zufriedenheit wurde von 96,4% (27/28) der Patientinnen angegeben. Schlussfolgerung: Der Einsatz der porcinen Gewebematrix Strattice® in der Brustrekonstruktion ist eine effektive und komplikationsarme Methode zur Deckung des Implantates nach skin-sparing Mastektomie.

Fragestellung: Erhohte Lokalrezidivraten bei nach neoadjuvanter Chemotherapie brusterhaltend operiertem Mammakarzinom sind Gegenstand des wissenschaftlichen Diskurses. In der vorliegenden Studie wurden die In-Brust-Rezidivraten nach neoadjuvanter Anbehandlung, intraoperativem Tumorbett-Boost mit Elektronen (IOERT) und nachfolgender Ganzbrustbestrahlung (WBRT) evaluiert. Methode: Im Zeitraum Janner 2002 bis Dezember 2007 wurden 84 Patientinnen im klinischen Stadium II oder III identifiziert, die vor der brusterhaltenden Operation mit axillarer Dissektion eine neoadjuvante Chemotherapie mit 3–6 Zyklen eines Anthrazyklin/Taxane haltigen Schemas erhalten hatten. Intraoperativ wurde ein Single-shot Boost des Tumorbetts mit Elektronen in der Hohe von 10Gy im Dosismaximum vorgenommen, gefolgt von einer Ganzbrustbestrahlung in konventioneller Fraktionierung mit 51–57Gy. Die Zeitspanne zwischen IOERT und WBRT betrug im Mittel 7,5 (3,7–23,6) Wochen, da keine adjuvante Chemotherapie mehr folgte. Ergebnisse: Bei 18/84 (21%) Patientinnen wurde eine komplette pathologische Remission erzielt. Das resezierte Volumen des Mammaparenchyms betrug im Mittel 250ml. Nach einem medianen FUP von 49 Monaten (7,6–100) wurde ein In-Brust-Rezidiv (In-Quadrant) detektiert. Zwei Patientinnen entwickelten ein regionares axillares Rezidiv, weitere neun Patientinnen Fernmetastasen, von denen sieben an der Tumorerkrankung verstorben waren. Bei drei Patientinnen trat ein kontralaterales Mammakarzinom auf. 69 Patientinnen (83%) sind tumorfrei. Es wurde somit ein metastasenfreies Uberleben (MFS), krankheitsfreies Uberleben (DFS) sowie ein Gesamtuberleben von 86,3%, 82,6% und 94,4% erzielt. Die gesamte In-Brustkontrollrate lag bei 93%. Schlussfolgerung: Im mittelfristigen Follow-Up fuhrt die Integration der IOERT auch nach neoadjuvanter Chemotherapie zu exzellenten In-Brust-Tumorkontrollraten, in Analogie zu den Ergebnissen bei primar operativem Vorgehen.

Surgical and systemic treatment modalities for breast cancer (BC) patients with micrometastatic disease in the sentinel lymph node biopsy (SNB) are controversial. The aim of this study was to evaluate decisional factors associated with assignment of adjuvant chemotherapy (CT).In a retrospective multicentric European study we evaluated cases of primary BC patients who underwent SNB. Logistic regression (LR) and recursive partitioning analyses (RPA) were performed to determine factors associated with CT.Of the 172 patients with micrometastatic disease, 39.5% received adjuvant CT. In the group treated with CT, patients tended to be younger (P = 0.001), with higher grade (P = 0.001) and HER2 positive tumors (P = 0.006) compared to patients without CT. In multivariate LR, age (P = 0.0027), high grading (P = 0.01) HER2 positivity (P = 0.03), and positive non-SN status (P = 0.03) were significantly associated with CT. RPA demonstrated that tumor grade, and not the non-SN status, was the first split in the partition tree followed by HER2 status, and non-SN status influencing the probability for CT administration.High tumor grade is the main decisional factor followed by HER2 positivity and then by the positive non-SN status for CT in micrometastatic disease in the SN.

Background: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status. Patients and methods: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease. Results: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR−) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%). Conclusions: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR−/HER2+ breast cancers.

The current study examined predictors of mastectomy in a certified breast center with the main impact on the factor surgeon. A total of 663 patients were analyzed for their mastectomy rates. Included were patients with T1 and T2 tumors, who had their surgery performed by one of three specialized breast surgeons with a workload of at least 50 new breast cancer cases per year. On multivariate analysis central tumor localization, positive lymph node status, nonunifocality, large tumor size, and the surgeon were independent predictors of mastectomy. Surgeon A had a mastectomy rate of 30.5% (50/164), surgeon B 26.9% (43/160) respectively, and surgeon C had a mastectomy rate of 15.8% (27/171), p = 0.005. Patients, who had surgery performed by surgeon A or surgeon B were 2.34 [95% confidence interval (CI): 1.38-3.97, p < 0.005] respectively 1.96 (95% CI: 1.14-3.36, p = 0.01) times as likely to have a mastectomy than patients who had surgery performed by surgeon C. Even in a certified breast center with specialized breast surgeons the surgeon is an independent risk factor of mastectomy, as the tumor criteria are given at the time of diagnosis.

Purpose To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response. Patients and Methods Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses. Results RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort. Conclusion RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.

Purpose To determine whether residual ductal carcinoma in situ (DCIS) after completion of preoperative chemotherapy affects the outcome of patients with histologically defined complete eradication of invasive cancer. Patients and Methods Retrospective analysis of a database including 2,302 breast cancer patients treated with neoadjuvant chemotherapy at The University of Texas M.D. Anderson Cancer Center between 1980 and 2004 was performed. The overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were compared for patients with no residual invasive or in situ cancer (pathologic complete response [pCR]) and patients with no residual invasive cancer but persistent in situ disease (pCR+DCIS). Results The mean follow-up time was 250 months. Of the 2,302 treated patients, 78 (3.4%) had pCR, 199 (8.6%) had pCR+DCIS, and 2,025 (88%) had residual invasive cancer. For patients with pCR and pCR+DCIS, the 5-year DFS rates (87.1% in both groups) and 10-year DFS rates (81.3% v 81.7%, respectively) were similar; the 5-year OS rates (91.9% v 92.5%, respectively) and 10-year OS rates (91.8% v 92.5%, respectively) were also similar and significantly better than the rate of patients with residual invasive cancer (74.4%; P < .001). The 5-year locoregional recurrence-free survival rates were also not different between patients with pCR (92.8%; 95% CI, 86.1% to 96.4%) and patients with pCR+DCIS (90.9%; 95% CI, 77.3% to 96.5%; P = .63). Conclusion Residual DCIS in patients who experience complete eradication of the invasive cancer in the breast and lymph nodes does not adversely affect survival or local recurrence rate. Inclusion of patients with residual DCIS in the definition of pCR is justified when this outcome is used as an early surrogate for long-term survival.