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The use of neoadjuvant chemotherapy (NAC) in patients with operable breast cancer allows for assessment of treatment response and subsequent tailoring of adjuvant therapy. Data are limited with respect to outcomes among patients with a heavy residual tumor burden after NAC. We report outcomes in patients who had exceptionally poor responses to NAC: those with9 involved nodes after NAC or with 5 cm or more of residual disease in the breast.Between June 2014 and April 2020, 1511 patients with breast cancer received NAC followed by surgery at our institution. Poor responders, defined as those with positive nodes or residual tumor in the breast, were identified for analysis. Patients were further classified into 3 groups for comparison purposes: (1) 1 to 3 positive nodes; (2) 4 to 9 positive nodes; or (3)9 positive nodes and/or5 cm of residual tumor, which was defined as high-volume residual (HVR). Recurrence and survival outcomes were compared based on residual disease burden after NAC.Among 934 poor responders, 539 patients had 1 to 3 positive nodes (ypN1), 215 had 4 to 9 positive nodes (ypN2), and 180 had HVR disease. Specifically, 118 had9 positive nodes (HVR), and 62 patients had5 cm of residual tumor in the breast. With a median follow-up of 31 months (interquartile range, 18-46), the 5-year overall survival rate was 88% among ypN1, 76% among ypN2, and 72% among patients with HVR disease (P.001). The 5-year distant recurrence-free survival and locoregional recurrence incidences were 82% and 7.6% among ypN1 versus 67% and 8.4% among ypN2 versus 53% and 12% among HVR, respectively.Our work suggests that patients with HVR disease are at high risk for locoregional and distant recurrence as well as death, despite best available standard-of-care treatment. Intensification of locoregional therapies and/or alternative adjuvant systemic treatment may improve outcomes in these poor responders.

Purpose/Objective(s) Following breast conserving surgery, the risk of ipsilateral in-breast recurrence is equivalent between whole breast radiation therapy (WBRT) and accelerated partial breast irradiation (APBI) in patients with low-risk tumors according to ASTRO guidelines. The Oncotype DX Recurrence Score (RS) is prognostic for both local and distant recurrence in ER+/HER2- breast cancer. Whether the RS can identify patients at increased risk for local recurrence among those considered eligible for APBI is unclear. Materials/Methods We retrospectively identified consecutive patients with clinical T1-2, ER+/HER2-, node-negative tumors with an available RS, and who were treated with APBI from 2010-2019 at a single institution. RS testing was performed for all patients with ER+/HER2-, invasive cancers ≥ 0.5 cm who were candidates for chemotherapy. Patients were considered for APBI based on the 2009 ASTRO guidelines. Characteristics were compared between patients with RS ≤ 25 and RS > 25 using Fisher's exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. The 6-year cumulative incidence rate (CIR) of local recurrence was estimated using Kaplan-Meier methods and was compared between groups using the log-rank test. Results 223 patients were identified; the median (IQR) age was 63 years (57-68) and median (IQR) tumor size was 1.0 cm (0.8-1.4). 201 patients (90%) had RS ≤ 25 and 22 patients (10%) had RS > 25. Nine patients aged ≤ 50 years were included, all of whom had RS ≤ 25. Compared with the RS ≤ 25 group, patients with RS > 25 more frequently had tumors that were progesterone receptor negative (55% vs. 9%; P 25 group (97% vs. 95%; P = 0.39), as was median (IQR) duration of endocrine therapy at 3 years (2-5) for both groups (P = 0.9). The median (range) follow-up was 3.6 years (0.1-10.2) and was similar between groups (P = 0.64). Overall, 4 ipsilateral in-breast recurrences occurred during follow-up, with 2 events (1.0%) in the RS ≤ 25 group and 2 events (9.1%) in the RS > 25 group (P = 0.05). The 6-year CIR of local recurrence was higher among patients with RS > 25 compared with RS ≤ 25 (6-year CIR [95% CI] 0.01 [0-0.04] vs. 0.08 [0-0.21]; P = 0.006). Due to a low number of events, a multivariable analysis of factors associated with local recurrence could not be performed. Conclusion The overall risk of local recurrence following APBI in patients with early-stage, ER+ tumors is low, but our findings suggest that the RS may identify patients at increased risk for local failure among a favorable risk population. Prospective studies are needed to assess whether genomic profiling can be used for additional risk stratification for patients considered eligible for APBI, to identify patients for whom de-escalation of WBRT may not be advisable.

PURPOSE/OBJECTIVE(S) The use of neoadjuvant chemotherapy (NAC) in patients with operable breast cancer allows for assessment of treatment response, and subsequent tailoring of adjuvant therapy. While there is robust evidence demonstrating worse prognosis with residual disease versus path CR after NAC, there is little data regarding outcomes among patients with a heavy residual tumor burden after NAC. We report outcomes in patients who have exceptionally poor responses to NAC-those with > 9 nodes after NAC or with 5 cm or more of residual disease in the breast. MATERIALS/METHODS Between 06/2014 and 04/2020, 1511 patients received NAC followed by surgery at our institution. Poor responders, defined as those with positive nodes or residual tumor in the breast, were identified for analysis. Those with 1-3 positive nodes after NAC were used as a comparison cohort. Recurrence and survival outcomes were compared based on residual disease burden after NAC. Clinicopathologic parameters were summarized with descriptive statistics. Overall survival and recurrence-free survival estimates were calculated using Kaplan Meier methodology. RESULTS Among 517 poor-responders, 315 patients had 1-3 positive nodes (N1a), 108 had 4-9 positive nodes (N2a), and 62 had > 9 positive nodes (high-volume residual, HVR); 32 patients with > 5cm of residual tumor in the breast were categorized as HVR. With a median follow-up of 39 months (IQR 27-50), the 5-year overall survival rate was 90% among N1a, 72% among N2a, and 78% among HVR patients (P = 0.003). The 5-year distant recurrence-free survival and local recurrence-free survival rates were 87%/87% among N1a vs. 59%/71% among N2a vs. 68%/75% among HVR (P < 0.001 and P = 0.009), respectively. 5-year local-regional and distant recurrence cumulative incidence rates, stratified by residual disease burden and by breast cancer subtype, are shown in Table 1. CONCLUSION Our work confirms that patients with high-volume residual are at high risk for LR and distant recurrence as well as death, despite best available standard-of-care treatment. ypN2a patients appear to perform as bad as HVR patients in terms of DM and death, but better in terms of local-regional recurrence. Triple-negative patients with residual disease had high rates of recurrence and death compared to other subtypes. Treatment intensification efforts are urgently needed.

Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy.Female patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan-Meier methodology.A total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P.001), estrogen receptor positivity (HR 0.64, P = .015), receipt of adjuvant chemotherapy (HR 0.52, P = .035), and black race (HR 2.87, P.001). The ultra-young were more likely to experience local failure compared with the aged 36 to 50 group (HR 2.2, 95% CI 1.8-2.6, P.001) and aged 51 to 70 group (HR 3.1, 95% CI 2.45 - 3.9, P.001). The cumulative incidence of secondary malignancies at 5 and 10 years was 2.2% and 4.4%, respectively. Receipt of radiation was not significantly associated with secondary malignancies or contralateral breast cancer.Survival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy.

PURPOSE: To evaluate patient experiences with decisions regarding radiation therapy (RT) for ductal carcinoma in situ (DCIS), and to assess clinician views on the role of RT for DCIS with favorable features in the present era. METHODS AND MATERIALS: A sample of women with newly diagnosed breast cancer from the population-based Georgia and Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registries were sent surveys approximately 2 months after undergoing breast-conserving surgery (BCS), with a 70% response rate. The analytic sample was limited to 538 respondents with unilateral DCIS. We also surveyed 761 surgeons and radiation oncologists treating breast cancer in those regions, of whom, 539 responded (71%). RESULTS: After BCS, 23% of patients omitted RT, with twice the rate of omission in Los Angeles County relative to Georgia (31% vs 16%; P < .001). The most common reasons for omitting RT were advice from a clinician that it was not needed (62%) and concern about side effects (24%). Cost and transportation were not reported as influential considerations. After covariate adjustment, low- and intermediate-grade disease (odds ratio [OR] 5.5, 95% confidence interval [CI] 2.5–12; and OR 3.2, 95% CI 1.7–6.1, respectively) and Los Angeles County SEER site (OR 4.3, 95% CI 2.3–8.2) were significantly associated with greater RT omission. Of the responding clinicians, 62% would discuss RT omission for a patient with DCIS with favorable features. Clinicians in Los Angeles County were more likely to discuss RT omission than were those in Georgia (67% vs 56%; P = .01). Approximately one third of clinicians would obtain the Oncotype DX DCIS score. CONCLUSIONS: The heterogeneity in RT omission after BCS for DCIS continues to be substantial, with systematic differences in provider opinions across the 2 regions we studied. Enhanced precision of recurrence estimates, guidance from professional organizations, and better communication are needed to improve the consistency of treatment in this controversial area.

Purpose The Patterns of Care Study performed this first known practice survey to establish a national profile of the delivery of postmastectomy radiotherapy (RT) in operable breast cancer. Methods and materials A Patterns of Care Study research associate collected data from 55 randomly selected institutions. The survey data included 132 items describing the patient, pathologic features, and treatment course for patients with clinical Stage I, II, and IIIA breast cancer undergoing postmastectomy RT in 1998 and 1999. A multivariate analysis was performed to determine the impact of tumor factors and type of treatment facility on the radiation fields used. Results A weighted sample size of 13,720 was obtained from a sampling of 405 patient records. The mean tumor size was 3.5 cm, and the mean number of axillary nodal metastases was 4.55. Lymphatic vascular invasion was noted in 34%, microscopic skin or dermal lymphatic invasion in 16%, positive or close margins in 36%, and extracapsular nodal extension in 23%. Radiotherapy included the chest wall in all cases and the regional nodes in 78%. When nodal RT was delivered, it included a supraclavicular field, supplemental axillary field, and/or an internal mammary field in 98%, 46%, and 23% of cases, respectively. Chest wall and supraclavicular RT was delivered in >90% of instances with 6-MV photons to doses between 45 and 50 Gy. More variation was seen in the delivery of the axillary and internal mammary RT. On multivariate analysis, the presence of four or more positive nodes and treatment at a large-volume facility were the factors most frequently associated with the use of regional radiation fields. Conclusion This Patterns of Care Study survey has demonstrated that breast cancer patients undergoing postmastectomy RT in 1998 and 1999 had a high proportion of factors associated with an increased risk of locoregional failure. The practice patterns established in this study provide a baseline for comparison with future survey results.

Purpose To assess whether radiation oncologists and surgeons differ in their attitudes regarding the local management of breast cancer, and to examine coordination of care between these specialists. Methods and Materials We surveyed attending surgeons and radiation oncologists who treated a population-based sample of patients diagnosed with breast cancer in metropolitan Detroit and Los Angeles. We identified 419 surgeons, of whom 318 (76%) responded, and 160 radiation oncologists, of whom 117 (73%) responded. We assessed demographic, professional, and practice characteristics; challenges to coordinated care; and attitudes toward management in three scenarios. Results 92.1% of surgeons and 94.8% of radiation oncologists indicated access to a multidisciplinary tumor board. Nevertheless, the most commonly identified challenge to radiation oncologists, cited by 27.9%, was failure of other providers to include them in the treatment decision process early enough. Nearly half the surgeons (49.7%) stated that few or almost none of the breast cancer patients they saw in the past 12 months had consulted with a radiation oncologist before undergoing definitive surgery. Surgeons and radiation oncologists differed in their recommendations in management scenarios. Radiation oncologists were more likely to favor radiation than were surgeons for a patient with 3/20 lymph nodes undergoing mastectomy ( p = 0.03); surgeons were more likely to favor more widely clear margins after breast conservation than were radiation oncologists ( p = 0.001). Conclusions Despite the widespread availability of tumor boards, a substantial minority of radiation oncologists indicated other providers failed to include them in the breast cancer treatment decision-making process early enough. Earlier inclusion of radiation oncologists may influence patient decisions, and interventions to facilitate this should be considered.

Purpose The purpose of this study was to evaluate the likelihood of complications and cosmetic results among breast cancer patients who underwent modified radical mastectomy (MRM) and breast reconstruction followed by radiation therapy (RT) to either a temporary tissue expander (TTE) or permanent breast implant (PI). Methods and Materials Records were reviewed of 74 patients with breast cancer who underwent MRM followed by breast reconstruction and RT. Reconstruction consisted of a TTE usually followed by exchange to a PI. RT was delivered to the TTE in 62 patients and to the PI in 12 patients. Dose to the reconstructed chest wall was 50 Gy. Median follow-up was 48 months. The primary end point was the incidence of complications involving the reconstruction. Results There was no significant difference in the rate of major complications in the PI group (0%) vs. 4.8% in the TTE group. No patients lost the reconstruction in the PI group. Three patients lost the reconstruction in the TTE group. There were excellent/good cosmetic scores in 90% of the TTE group and 80% of the PI group (p = 0.22). On multivariate regression models, the type of reconstruction irradiated had no statistically significant impact on complication rates. Conclusions Patients treated with breast reconstruction and RT can experience low rates of major complications. We demonstrate no significant difference in the overall rate of major or minor complications between the TTE and PI groups. Postmastectomy RT to either the TTE or the PI should be considered as acceptable treatment options in all eligible patients.

Results: A total of 53,431 articles were screened, with consensus from both investigators on the articles included. In total, 10 clinical studies met inclusion criteria, with 268 patients treated by ablative therapies for MBC. Fourteen patients were treated with metastasectomy, 82 with radioembolization with Yttrium-labelled microspheres, 48 with radiofrequency ablation, 89 with SRS/SBRT, and 35 with a combination of SRS/SBRT and metastasectomy. Median OS was 28 months (range 8.2-60) amongst the reported studies. In 2 studies, median OS was not reached. PFS was poorly reported, but varied from 26% to 80% at 4-5-years. Initial analysis demonstrated improved PFS and OS in patients with limited metastatic lesions, disease confined to a single organ, and management with localized therapies as opposed to systemic treatment alone. Conclusion: MBC patients treated with ablative therapies represent a heterogeneous population that can benefit from long term PFS and OS when presenting with limited disease burden. The best predictors of PFS and OS were the number of metastatic lesions and single organ involvement, encouraging the consideration of these variables in future studies. Comparison of survival estimates versus trials using systemic therapy alone is warranted in order to determine the minimal clinically important differences for future randomized trial design. Author Disclosure: M.J. Kucharczyk: None. A. Swaminath: None.

Purpose: Standard radiation for early breast cancer requires daily treatment for 6 to 7 weeks. This is an inconvenience to many women, and for some a barrier for breast conservation. We present the acute toxicity of a 4-week course of hypofractionated radiation. Methods and Materials: A total of 75 patients completed radiation on a Phase II trial approved by the hospital institutional review board. Eligibility criteria were broad to include any patient normally eligible for standard radiation: age ≥18 years, invasive or in situ cancer, American Joint Committee on Cancer Stage 0 to II, breast-conserving surgery, and any systemic therapy not given concurrently. The median age was 52 years (range, 31–81 years). Of the patients, 15% had ductal carcinoma in situ , 67% T1, and 19% T2; 71% were N0, 17% N1, and 12% NX. Chemotherapy was given before radiation in 44%. Using photon intensity-modulated radiation therapy and incorporated electron beam boost, the whole breast received 45 Gy and the lumpectomy bed 56 Gy in 20 treatments over 4 weeks. Results: The maximum acute skin toxicity by the end of treatment was Grade 0 in 9 patients (12%), Grade 1 in 49 (65%) and Grade 2 in 17 (23%). There was no Grade 3 or higher skin toxicity. After radiation, all Grade 2 toxicity had resolved by 6 weeks. Hematologic toxicity was Grade 0 in most patients except for Grade 1 neutropenia in 2 patients, and Grade 1 anemia in 11 patients. There were no significant differences in baseline vs. 6-week posttreatment patient-reported or physician-reported cosmetic scores. Conclusions: This 4-week course of postoperative radiation using intensity-modulated radiation therapy is feasible and is associated with acceptable acute skin toxicity and quality of life. Long-term follow-up data are needed. This radiation schedule may represent an alternative both to longer 6-week to 7-week standard whole-breast radiation and more radically shortened 1-week, partial-breast treatment schedules.

The relationship between benign breast disease and breast cancer has become the focus of increased clinical attention as breast cancer prevention becomes a clinical reality. In this setting an understanding of the magnitude of the increase in risk conferred by the various types of benign breast disease assumes increasing importance. When benign breast disease is considered as an aggregate, estimates of the relative risk of breast cancer development range from 0.8 to 4.5. This article describes the risk associated with proliferative and non-proliferative benign breast disease, as well as the rationale for considering lobular carcinoma in situ and ductal carcinoma in situ (in some cases) as risk factors for breast carcinoma rather than actual malignant lesions. Mathematical models can provide a more precise estimate of breast cancer risk, but these efforts may be confounded by the lack of uniformity in the pathologic definition of borderline benign breast lesions. The breast cancer prevention trials offer a unique opportunity to improve our database on the natural history of high risk benign breast lesions, while attempting to reduce the 44,000 deaths occurring annually from breast cancer.

positive patients were randomized to receive tamoxifen or placebo (3). In both of these studies, local failure rates in patients receiving systemic therapy were approximately half those of patients not receiving such therapy. The failure to receive adjuvant therapy was identified by Fein et al. (2) as a factor that significantly influenced breast recurrence and might account for some of the differences observed between patients with and without clips. The other significant predictor of breast recurrence in this study was a particular surgeon. At first glance, this information does not seem to be too useful for those who do not interact with this individual. However, the surgeon in question failed to ink specimen margins in one half of the cases, and the high breast recurrence rates observed in these patients serve to emphasize the importance of accurate margin assessment in determining the extent of surgery necessary for local control. Microscopic residual carcinoma is present in between 30% and 48% of patients with clinically localized carcinoma who undergo tumor excision with negative margins ( 1, 10, 12). In patients with positive or unknown margins, residual tumor is present in 42% to 69% of cases (4, 7, lo), and macroscopic residual disease is more likely than in cases with negative margins. The likelihood of residual carcinoma does not differ between cases with positive and unknown margins, and in 90% of cases is located within 4 cm of the index tumor (6). A gross determination of margin status by the surgeon or the pathologist is inadequate to identify microscopic residual disease, and cases in which margins have not been inked should be re-excised. The routine inking of breast biopsy specimens will avoid the need for re-excision in many cases. We have demonstrated that the routine use of magnification mammography to define the extent of the primary tumor coupled with an attempt to remove a gross margin of 0.5- 1 .O cm of normal breast tissue around the tumor at the time of diagnostic biopsy results in negative margins in 95% of cases without compromising cosmesis in patients with benign disease (7, 8).