Background. Conflicting data exist regarding optimum local therapy for early-stage triple-negative breast cancer (TNBC). We examined outcomes according to local treatment type in a large cohort of node-negative TNBC patients. Methods. A total of 1,242 consecutive patients with TNBC treated at a single institution from 1999 to 2008 were identified. Of these, 646 with pathologic stage T1-2N0 TNBC underwent breast-conserving therapy (BCT) (N = 448) or total mastectomy (TM) without postmastectomy radiation (N = 198) and comprised the study population. Locoregional recurrence (LRR), distant metastasis (DM), and overall recurrence were investigated with a competing risk analysis using Gray's test and multivariable Fine and Gray competing risk regression. Overall survival was assessed using standard Kaplan-Meier methods and a Cox proportional hazards analysis. Results. Median follow-up was 78.3 months (range 1-156). Eight-one percent of patients received adjuvant chemotherapy. TM patients were younger, were more likely to have lymphovascular invasion, and had larger tumors than patients undergoing BCT (all P B 0.05). The 5-year cumulative incidence of LRR was 4.2 and 5.4 % for patients undergoing BCT and TM, respectively. There was no significant difference in LRR, DM, overall recurrence, disease free survival, or overall survival between groups on univariate analysis, or after adjusting for other variables in multivariate models. Lack of chemotherapy and high tumor stage independently predicted for decreased overall survival (both P \ 0.001). Conclusions. A low, 5-year risk of LRR (4.7 %) was achieved in a large group of women with T1-2N0 TNBC treated with multimodality therapy. BCT was as equally effective as TM for local and distant control.The poor prognosis of triple-negative breast cancer (TNBC) relative to other biologic subtypes of breast cancer has been well established during the past decade.

BACKGROUND:The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. METHODS: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival. RESULTS: The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported. CONCLUSIONS: The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triplenegative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed. Cancer 2020;126:850-860.

No abstract

Early-stage breast cancer patients with minimal sentinel node disease experience excellent outcomes without ALND, whether they undergo BCS or TM.

Background: Multi-beam IMRT enhances the therapeutic index by increasing the dosimetric coverage of the targeted tumor tissues while minimizing volumes of adjacent organs receiving high doses of RT. The tradeoff is that a greater volume of lung is exposed to low doses of RT, raising concern about the risk of radiation pneumonitis (RP).Methods: Between 7/2010-1/2013, patients with node-positive breast cancer received inverseplanned, multibeam IMRT to the breast/chest wall and regional nodes including the internal mammary nodes (IMN). The primary endpoint was feasibility, predefined by dosimetric treatment planning criteria. Secondary endpoints included the incidence of ≥ grade 3 RP and changes in pulmonary function measured by CTCAE v3.0 scales, pulmonary function tests (PFTs) and

Triple-negative breast cancer (TNBC) disproportionately affects black women. However, black race as a prognostic factor in TNBC has not been well studied. We evaluated the effect of race, among other variables, on outcomes in women with TNBC. A total of 704 patients with stages I-III TNBC treated with breast-conserving surgery ± adjuvant radiation therapy (RT) and chemotherapy were identified from an institutional database. Competing risk analyses, Kaplan-Meier methods, and Cox proportional hazards models identified associations among clinicopathologic variables on locoregional recurrence (LRR), distant recurrence (DR), and overall survival (OS). LRR was defined as a biopsy proven, triple receptor-negative recurrence in the ipsilateral breast or regional lymph nodes. At a median follow-up of 51 months, there were 55 LRR, 61 DR, and 111 death events. Compared to non-black women, black women had higher disease stage and were more likely to receive axillary lymph node dissection, chemotherapy, and nodal irradiation (all P < 0.05). After adjustment for stage, age, lymphovascular invasion, chemotherapy, and RT on multivariate analysis, black race was prognostic for increased risk of LRR (hazard ratio [HR] = 3.17; 95 % confidence interval: 1.7-5.8; P = 0.0002). The 5-year risk of regional recurrence was higher in black women (10 vs. 2 %, P < 0.0001), but local failures were similar between groups (3.0 vs. 5.3 %, P = 0.15). RT was an independent predictor for decreased LRR and increased OS on multivariate analyses (P = 0.0006 and P = 0.0003, respectively). Black women with TNBC had equivalent local control, but higher risk of regional nodal failure, compared with non-black counterparts. The routine use of comprehensive nodal irradiation may be beneficial for black women with TNBC.

14 Background: Overall response rates of 13-19% have been reported with checkpoint inhibitor monotherapy in chemotherapy-resistant, PD-L1-positive mTNBC. RT is frequently used to enhance local control in mTNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. In this study, we evaluate the safety and efficacy of RT combined with a programmed cell death protein 1 (PD-1) inhibitor, pembro, in a single-arm, two-stage, phase II study in mTNBC. Methods: Eligible women had biopsy-proven mTNBC, ECOG performance status 0-2, and ≥2 measurable sites of metastatic disease with at least one site requiring RT. A total RT dose of 3000 cGy was delivered in 5 daily fractions. Pembro 200 mg was given intravenously within 3 days of first RT fraction, then every 3 weeks +/-3 days until disease progression. The primary endpoint was overall response rate at week 13 in the non-irradiated lesions by RECIST v1.1. Secondary endpoints included safety and overall survival. Tumor biopsies were obtained at baseline and at week 7. PD-L1 expression was not required for study entry. Results: Of the 17 women enrolled, the median age was 52 y (range 37-73y). and the median number of prior chemotherapies received for metastatic disease was 3 (range 0 to 8). Of the 8 women not evaluable at 13 weeks: 5 died secondary to disease-related complications (at weeks 2, 6, 7, 8, and 9) and 3 came off study due to disease progression prior to week 13. Of the 9 women evaluable at week 13, 3 (33%) had a partial response, 1 (11%) had stable disease and 5 (56%) had disease progression. The 3 partial responses represented 60%, 54%, and 34% decreases in tumor burden by RECIST v1.1 and were durable for 31, 21, and ongoing at 22 weeks, respectively. The stable disease response was durable for 22 weeks. Common toxicities were mild and included fatigue, myalgia and nausea. Conclusions: The combination of pembro and RT is well-tolerated. This is a poor prognosis population with 5/17 (29%) of patients dying within 12 weeks of study entry. However, durable responses were observed outside of the RT field in 3/9 (33%) patients who were unselected for PD-L1 expression and evaluable at 13 weeks. Clinical trial information: NCT02730130.

No abstract