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Purpose: Human epidermal growth factor receptor 2 (HER2)-directed therapy improves local control among women with HER2-positive breast cancer. This retrospective analysis evaluates the safety and efficacy of radiation therapy (RT) among patients receiving adjuvant trastuzumab emtansine (T-DM1) or paclitaxel (T) plus trastuzumab (H) in the ATEMPT (Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab) trial; Translational Breast Cancer Research Consortium (TBCRC) 033.Methods and Materials: Patients with stage I HER2-positive breast cancer were randomized 3:1 to receive adjuvant T-DM1 or TH after mastectomy or breast-conserving surgery (BCS). Breast RT was required after BCS and permitted after mastectomy. Patients receiving T-DM1 began RT after 12 weeks of therapy and received RT concurrently with T-DM1. Patients receiving TH began RT after paclitaxel, but concurrent with trastuzumab. RT records were retrospectively reviewed to determine details of radiation delivery and acute RT-related toxicity.Results: Protocol therapy was initiated by 497 patients. Among the 299 BCS patients, 289 received whole breast RT (WBRT) and 10 partial breast. Among WBRT patients, 40.2% in the T-DM1 arm and 41.5% of TH patients received hypofractionated (≥2.5 Gy/fraction) RT. Eight mastectomy patients received RT, all conventional fractionation. Skin toxicity (grade ≥2) was seen in 33.9% of patients in the T-DM1 arm and 23.2% in the TH arm (P = .11). In conventionally fractionated WBRT patients, 44.7% had a grade ≥2 skin toxicity compared with 17.9% of patients receiving hypofractionation (P < .001). Five patients experienced pneumonitis after RT (T-DM1: n = 4, 1.0%; TH: n = 1, 0.9%). Three-year invasive disease-free survival was 97.8% for T-DM1 (95% confidence interval, 96.3-99.3) and 93.4% for TH (95% confidence interval, 88.7-98.2). Among the 18 invasive disease-free survival events, 7 were isolated locoregional recurrences (2, T-DM1; 5, TH).Conclusions: RT was well-tolerated when given concurrently with either T-DM1 or TH. Among BCS patients, hypofractionation resulted in lower grade ≥2 acute skin toxicity even with concurrent anti-HER2 therapy. Although follow-up was short, local recurrences were uncommon, attesting to the efficacy of HER2-directed therapy combined with RT. [ABSTRACT FROM AUTHOR]

Purpose: Patients with triple-negative breast cancer (TNBC) experience higher local-regional recurrence rates than those with luminal or HER2-positive tumors. This prospective, phase 1B trial was designed to assess the safety and to establish the maximum tolerated dose (MTD) of cisplatin with radiation therapy for women with early-stage TNBC.Methods and Materials: Eligible patients had stage II or III TNBC. Cisplatin was initiated at 10 mg/m2 intravenously once weekly during radiation and then escalated in a 3 + 3 design by 10 mg/m2 at each dose level until 40 mg/m2, or the MTD, was reached. Patients undergoing breast-conserving therapy (BCT) or mastectomy were accrued in separate parallel cohorts during dose escalation, followed by a 10-patient expansion at the MTD.Results: During 2013 to 2018, 55 patients were accrued. Four patients developed dose-limiting toxicity. In the BCT cohort, 1 patient receiving 40 mg/m2 developed tinnitus resulting in a cisplatin delay; therefore, this was the BCT cohort MTD. In the mastectomy cohort, 1 patient receiving 20 mg/m2 developed a grade 3 urinary infection, and 2 additional patients had dose-limiting toxicities at 40 mg/m2 (grade 3 neutropenia and grade 2 tinnitus), both resulting in cisplatin delay. Thus, 30 mg/m2 was the mastectomy cohort MTD. Median follow-up was 48.5 months. Three-year disease-free survival was 74.7% for the BCT cohort and 64.4% for the mastectomy cohort.Conclusions: Adjuvant radiation therapy with concurrent cisplatin is feasible with a recommended phase 2 dose of 30 mg/m2 and 40 mg/m2 intravenously weekly in mastectomy and BCT cohorts, respectively. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) exhibits dermal lymphatic involvement at presentation, and thus, the standard surgical approach is a nonskin‐sparing modified radical mastectomy (MRM) without breast reconstruction (BR). In this study, we evaluated immediate and delayed BR receipt and its outcomes in IBC. Using an IRB‐approved database, we retrospectively evaluated stage III IBC patients who received trimodality therapy (preoperative systemic therapy, followed by MRM and postmastectomy chest wall/regional nodal radiation). Patients with an insufficient response to preoperative systemic therapy and/or who required preoperative radiotherapy were excluded. BR receipt, timing, and morbidity were evaluated. Among 240 stage III IBC patients diagnosed between 1997 and 2016, 40 (17%) underwent BR. Thirteen (33%) had immediate, and 27 (67%) had delayed BR. Four patients had complications (1 [8%] immediate BR and 3 [11%] delayed BR); only 1 BR (delayed) was unsuccessful. From the MRM date, the median time to recurrence was 35 months (<1‐212) and median overall survival was 87 months (<1‐212). In this cohort of stage III IBC patients, only 11% pursued delayed BR following trimodality therapy, possibly attributable to the observed high recurrence rates hindering BR. Further studies addressing BR outcomes in IBC are needed for better counseling patients regarding their reconstructive options. [ABSTRACT FROM AUTHOR]

The article discusess a study conducted for examining patient‐preferred outcomes measurement after postmastectomy radiation therapy and immediate reconstruction which is an important measure of treatment success. It mentions that breast reconstruction followed by post‐mastectomy radiation therapy, patients selected a general outcome, physical well‐being, as the outcome of most importance to them.

Local-regional recurrence ( LRR) after breast-conserving therapy ( BCT) can result in distant metastasis and decreased disease-free survival ( DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor ( ER), progesterone receptor ( PR), human epidermal growth factor receptor 2 ( HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow-up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in-breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five-year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple-negative disease ( ER/ PR/ HER2 negative, TNBC) was associated with reduced DFS ( HR = 3.8; 95% CI: 1.8-8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size ( HR = 1.3; 95% CI: 1.03-1.6; p = 0.02), shorter interval from initial diagnosis to LRR ( HR = 0.98 per month; 95% CI: 0.97-0.99; p = 0.02), and no salvage surgery ( HR = 0.2; 95% CI: 0.09-0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS ( HR = 4.8; 95% CI: 2.25-10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis. [ABSTRACT FROM AUTHOR]

Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early-stage breast cancer. Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit. Although acute side effects of radiation therapy are generally well tolerated; efforts are ongoing to minimize the long-term side effects of radiation, most prominently atherosclerotic heart disease. Efforts to minimize radiation therapy are also underway. They include omitting treatment altogether in the elderly and using accelerated, hypofractionated whole-breast irradiation, and accelerated partial-breast irradiation. Several randomized studies are ongoing to determine the efficacy, safety, and appropriate patients for these shorter treatments. [ABSTRACT FROM AUTHOR]

HER2)-low expression is a predictive biomarker for novel anti-HER2 antibody-drug conjugates. However, little is known about its clinical significance in inflammatory breast cancer (IBC). Patients diagnosed with HER2-negative IBC between December 1999 and December 2020 were identified from the Dana-Farber Cancer Institute IBC registry. Patients were divided into HER2-low (IHC 1+ or 2+/ISH–) and HER2-zero (IHC 0), comparing clinicopathologic features and disease outcomes between the two subgroups. The study included 276 patients. Among patients with stage III (n = 209) and stage IV (n = 67) IBC, 54% and 39% had HER2-low tumours, respectively. Oestrogen receptor (ER)-expressing tumours were more common in patients with HER2-low versus HER2-zero stage III IBC (65% versus 38%, p < 0.01). Among stage III patients undergoing surgery (n = 182), pathologic complete response (pCR) rates were higher for HER2-zero versus HER2-low IBC (11% versus 6%, OR: 1.8, 95%CI:0.6–5.3), but minimal differences persisted when separately analysing pCR by ER status. Similar invasive disease-free survival (iDFS) outcomes were observed among ER-positive HER2-zero versus HER2-low IBC (48-month iDFS: 63% versus 63%, HR: 1.10, 95%CI:0.57–2.13) and ER-negative HER2-zero versus HER2-low IBC (48-month iDFS: 28% versus 25%, HR: 1.19, 95%CI:0.69–2.04). Differences in overall survival (OS) were small, both among ER-positive HER2-zero versus HER2-low IBC (48-month OS: 80% versus 81%, HR: 0.82, 95%CI:0.39–1.73) and ER-negative HER2-zero versus HER2-low IBC (48-month OS: 34% versus 47%, HR: 1.34, 95%CI: 0.74–2.41). Marginal differences in clinicopathologic features and outcomes were observed in HER2-low versus HER2-zero IBC when controlling for ER status, not supporting the definition of HER2-low as a distinct subtype of IBC. • Trastuzumab deruxtecan showed to prolong survival in HER2-low breast cancer (BC). • No data exist on the clinical role of HER2-low expression in inflammatory BC (IBC). • We found more ER-expressing tumours among stage III HER2-low (versus HER2-zero) IBC. • As in non-IBC, no clear prognostic role emerged for HER2-low expression in IBC. • Our results do not support HER2-low as a distinct subtype of IBC. [ABSTRACT FROM AUTHOR]

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this cross-sectional study was to characterize long-term breast pain in patients undergoing breast-conserving surgery and radiation (BCT) and to identify predictors of this pain.Methods and Materials: We identified 355 eligible patients with Tis-T2N0M0 breast cancer who underwent BCT in 2007 to 2011, without recurrent disease. A questionnaire derived from the Late Effects Normal Tissue Task Force (LENT) Subjective, Objective, Management, Analytic (SOMA) scale was mailed with 7 items detailing the severity, frequency, duration, and impact of ipsilateral breast pain over the previous 2 weeks. A logistic regression model identified predictors of long-term breast pain based on questionnaire responses and patient, disease, and treatment characteristics.Results: The questionnaire response rate was 80% (n=285). One hundred thirty-five patients (47%) reported pain in the treated breast, with 19 (14%) having pain constantly or at least daily; 15 (11%) had intense pain. The pain interfered with daily activities in 11 patients (8%). Six patients (4%) took analgesics for breast pain. Fourteen (10%) thought that the pain affected their quality of life. On univariable analysis, volume of breast tissue treated to ≥105% of the prescribed dose (odds ratio [OR] 1.001 per cc, 95% confidence interval [CI] 1.000-1.002; P=.045), volume treated to ≥110% (OR 1.009 per cc, 95% CI 1.002-1.016; P=.012), hormone therapy use (OR 1.95, 95% CI 1.12-3.39; P=.02), and other sites of pain (OR 1.79, 95% CI 1.05-3.07; P=.03) predicted for long-term breast pain. On multivariable analysis, volume ≥110% (OR 1.01 per cc, 95% CI 1.003-1.017; P=.007), shorter time since treatment (OR 0.98 per month, 95% CI 0.96-0.998; P=.03), and hormone therapy (OR 1.84, 95% CI 1.05-3.25; P=.03) were independent predictors of pain.Conclusion: Long-term breast pain was common after BCT. Although nearly half of patients had pain, most considered it tolerable. Dosimetric inhomogeneity independently predicted for pain and should be minimized to the greatest extent possible. [ABSTRACT FROM AUTHOR]