Nivolumab and Stereotactic Radiosurgery for Patients With Breast Cancer Brain Metastases: A Nonrandomized, Open-Label Phase 1b Study.

PURPOSE: We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone. METHODS AND MATERIALS: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT03807765. RESULTS: Between February 2019 and July 2020, a total of 12 patients were treated to 17 lesions. No dose limiting toxicities were noted in our patient population. The most common neurologic adverse events included grade 1 to 2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% confidence interval, 3-14 months) with 6- and 12-month control rates of 55% and 22%, respectively. A total of 4 patients had systemic progression during the study. Median time to systemic progression free survival has not been reached with 6- and-12 month rates of 63% and 51%, respectively. CONCLUSIONS: Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary data reveals activity in certain breast cancer patients to study therapy.

Real-world benefit of combination palbociclib and endocrine therapy for metastatic breast cancer and correlation with neutropenia.

BACKGROUND: Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real-world benefit of first-line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. METHODS: This study included HR-positive, HER2-negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression-free survival (PFS) was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time-dependent variable. RESULTS: In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93-NR). Median PFS for patients with bone-only metastases (n = 54) was not reached (95% CI 18.21-NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33-33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71-0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97-1.18, p = 0.203). CONCLUSION: The effectiveness of palbociclib and endocrine therapy in the treatment of HR-positive, HER2-negative mBC in the real-world setting is similar to the efficacy reported in the PALOMA-2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.

Is it Wise to Omit Sentinel Node Biopsy in Elderly Patients with Breast Cancer?

BACKGROUND: The Society of Surgical Oncology's Choosing Wisely® guidelines recommend against routine sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0), hormone receptor (HR)-positive breast cancer patients aged ≥ 70 years. We examined the effect of SLNB on treatment and outcomes in this population. MATERIALS AND METHODS: A single-institution retrospective review of consecutive cN0 women ≥ 70 years of age who received SLNB was performed. We collected clinicopathologic characteristics and treatment data. Patients were compared according to SLN status with subset analysis of HR-positive patients. Outcomes were analyzed using the Kaplan-Meier method and univariable analysis, and were compared using log-rank tests. RESULTS: Of 500 patients, 345 (69%) were SLN-negative. Median age was 74 years (range 70-96). Most tumors were T1 (72%), N0 (69%), invasive ductal (77%), without lymphovascular invasion (88%), estrogen receptor-positive (88%) and progesterone receptor-positive (75%), and human epidermal growth factor receptor 2 (HER2)-negative (88%) treated with lumpectomy (71%). Median number of SLNs obtained was 2 (range 0-12) and median number of positive SLNs was 0 (range 0-8). Characteristics of the HR-positive subset were similar. In both the overall cohort and the HR-positive subset, SLN status significantly affected the use of adjuvant chemotherapy, although no significant effect on recurrence was observed. SLN-negative patients had better overall survival and less distant recurrence (both p < 0.0001). Adjuvant hormone therapy significantly improved overall survival. CONCLUSIONS: SLNB can be safely omitted in elderly patients with T1, HR-positive, invasive ductal carcinoma tumors, but may still provide important information affecting treatment. Patients who are candidates for adjuvant systemic chemotherapy should still be considered for SLNB.

Breast Cancer Survivorship: Patient Characteristics and Plans for High-Quality Care.

The number of breast cancer survivors has increased and this increase is expected to continue, likely as a result of population and age growth, the implementation of earlier detection strategies, and the development of more effective therapies. Breast cancer treatment requires a multidisciplinary approach with surgery, radiation, chemotherapy, targeted therapy, and hormonal therapy. Breast cancer survivors may develop various long-term adverse effects from these therapies. Care of the survivor may transition eventually to the primary care physician. Survivorship care plans have been developed to facilitate care transition, guide the content and coordination of posttreatment care, and engender greater self-management of health by cancer survivors. Guidelines for posttreatment follow-up care are discussed in this article, and interventions that patients may practice to promote a healthy lifestyle also are presented.

Breast Cancer Risk Reduction, Version 2.2015.

Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.

Time to adjuvant chemotherapy for breast cancer in National Comprehensive Cancer Network institutions.

BACKGROUND: High-quality care must be not only appropriate but also timely. We assessed time to initiation of adjuvant chemotherapy for breast cancer as well as factors associated with delay to help identify targets for future efforts to reduce unnecessary delays. METHODS: Using data from the National Comprehensive Cancer Network (NCCN) Outcomes Database, we assessed the time from pathological diagnosis to initiation of chemotherapy (TTC) among 6622 women with stage I to stage III breast cancer diagnosed from 2003 through 2009 and treated with adjuvant chemotherapy in nine NCCN centers. Multivariable models were constructed to examine factors associated with TTC. All statistical tests were two-sided. RESULTS: Mean TTC was 12.0 weeks overall and increased over the study period. A number of factors were associated with a longer TTC. The largest effects were associated with therapeutic factors, including immediate postmastectomy reconstruction (2.7 weeks; P < .001), re-excision (2.1 weeks; P < .001), and use of the 21-gene reverse-transcription polymerase chain reaction assay (2.2 weeks; P < .001). In comparison with white women, a longer TTC was observed among black (1.5 weeks; P < .001) and Hispanic (0.8 weeks; P < .001) women. For black women, the observed disparity was greater among women who transferred their care to the NCCN center after diagnosis (P (interaction) = .008) and among women with Medicare vs commercial insurance (P (interaction) < .001). CONCLUSIONS: Most observed variation in TTC was related to use of appropriate therapeutic interventions. This suggests the importance of targeted efforts to minimize potentially preventable causes of delay, including inefficient transfers in care or prolonged appointment wait times.

Effects of self-directed stress management training and home-based exercise on quality of life in cancer patients receiving chemotherapy: a randomized controlled trial.

BACKGROUND: Research has shown that self-directed stress management training improves mental well-being in patients undergoing chemotherapy. The present study extends this work by evaluating separate and combined effects of stress management training and home-based exercise. METHOD: Following assessment of mental and physical well-being, depression, anxiety, exercise, and stress reduction activity before chemotherapy started, patients were randomized to stress management training (SM), exercise (EX), combined stress management and exercise (SMEX), or usual care only (UCO). Outcomes were reassessed 6 and 12 weeks after chemotherapy started. Significance testing of group-by-time interactions in 286 patients who completed all assessments was used to evaluate intervention efficacy. RESULTS: Interaction effects for mental and physical well-being scores were not significant. Depression scores yielded a linear interaction comparing UCO and SMEX (p = 0.019), with decreases in SMEX but not UCO. Anxiety scores yielded a quadratic interaction comparing UCO and SMEX (p = 0.049), with trends for changes in SMEX but not UCO. Additional analyses yielded quadratic interactions for exercise activity comparing UCO and SMEX (p = 0.022), with positive changes in SMEX but not UCO, and for stress management activity comparing UCO and SM (p < 0.001) and UCO and SMEX (p = 0.013), with positive changes in SM and SMEX but not UCO. CONCLUSION: Only the combined intervention yielded effects on quality of life outcomes, and these were limited to anxiety and depression. These findings are consistent with evidence that only the combined intervention yielded increases in both exercise and stress management activity. Future research should investigate ways to augment this intervention to enhance its benefits.

Breast cancer recurrence risk reduction beliefs in breast cancer survivors: prevalence and relation to behavior.

OBJECTIVE: There is a growing body of evidence suggesting breast cancer (BC) recurrence risk might be linked to behavioral factors. However, little is known about BC survivors' beliefs regarding the link between their behavior and recurrence risk. The objective of this study was to describe BC survivors' beliefs regarding performance of behaviors potentially associated with BC recurrence risk reduction, and to examine the link between these behaviors and BC recurrence risk reduction beliefs, worry, and risk perception. METHODS: 200 female BC survivors (age, years: mean=57.7, standard deviation=9.2) completed a questionnaire assessing beliefs about the effectiveness of 14 potential BC recurrence risk reduction behaviors, their performance of these potential risk reduction behaviors, recurrence worry, and perception of personal lifetime BC recurrence risk. RESULTS: The behaviors most frequently endorsed as potentially reducing BC recurrence risk included avoiding tobacco use (84%), exercising at least three times per week (74%), eating an average of five servings a day of fruits and vegetables (72%), and limiting food intake to maintain current weight or lose weight (70%). Multivariate logistic regression analyses predicting behavioral performance showed that beliefs were consistently associated with behavior while worry and risk perception were largely unrelated to behavior. CONCLUSIONS: BC survivors' beliefs about the effectiveness of potential BC recurrence risk reduction behaviors are largely consistent with empirical findings and relate strongly to actual behavioral performance. Misconceptions about the effects of behavior to reduce BC recurrence risk are important targets for clinical and public health efforts.