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Recent studies show that the prevalence of germline pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes in metastatic prostate cancer is higher than previously recognized and higher than in unaffected men. Specific gene dysfunction is important in prostate cancer initiation and/or evolution to metastases. This article reviews key literature on individual genes, recognizing BRCA2 as the gene most commonly altered in the metastatic setting. This article discusses the importance of representative and diverse inclusion, and efforts to advance management for at-risk carrier populations to maximize clinical benefit., Competing Interests: Disclosure A.O. Sokolova receives research funding from NIH/NCIT32CA009515. E.I. Obeid receives research funding from the American Cancer Society, Eileen Jacoby Foundation, Genetech, Merck, NCCN Foundation Young Investigator Award, and Newtown Foundation; and has a consultancy or advisory role to Daiichi Sankyo, Ethos Immunomedics, Foundation Medicine, Incyte, Novartis, OncLive, Pfizer, and Puma. H.H. Cheng receives research funding from the PNW SPORE CA097186, Prostate Cancer Foundation, NIH/NCI P30 CA015704, DOD W81XWH-17-2-0043; receives research funding to institution from Clovis Oncology, Club Foundation, Janssen, Medivation and Sanofi; has a consultancy role to AstraZeneca; and receives royalties from UpToDate. The authors have nothing else to disclose, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/objective: Delays in times to surgery, chemotherapy, and radiotherapy impair survival in breast cancer patients. Neoadjuvant chemotherapy (NAC) confers equivalent survival to adjuvant chemotherapy (AC), but it remains unknown which approach facilitates faster initiation and completion of treatment., Methods: Women ≥18 years old with nonrecurrent, noninflammatory, clinical stage I-III breast cancer diagnosed between 2004 and 2015 who underwent both surgery and chemotherapy were reviewed from the National Cancer Database., Results: Among 155 606 women overall, 28 241 patients received NAC and 127 365 patients received AC. NAC patients had higher clinical T and N stages (35.8% T3/4 vs 4.9% T3/4; 14.4% N2/3 vs 3.7% N2/3). After adjusting for stage and other factors, NAC patients had longer times to begin treatment (36.1 vs 35.4 days adjusted, P = .15), and took significantly longer to start radiotherapy (240.8 vs 218.2 days adjusted, P < .0001), and endocrine therapy (301.6 vs 275.7 days adjusted, P < .0001). Unplanned readmissions (1.2% vs 1.7%), 30-day mortality (0.04% vs 0.01%), and 90-day mortality (0.30% vs 0.08%) were all low and clinically insignificant between NAC and AC., Conclusion: Compared to patients receiving AC, those receiving NAC do not start treatment sooner. In addition, patients receiving NAC do not complete treatment faster. Although there are clear indications for administering NAC vs AC, rapidity of treatment should not be considered a benefit of giving chemotherapy preoperatively., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multi-gene panel tests is critical for providers on the front-line of women's health., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Randomized data examining adjuvant radiation therapy (RT) alone in elderly women with low-risk, hormone receptor-positive (HR(+)) breast cancer is lacking. We investigated the outcomes for elderly women treated with adjuvant RT alone versus RT plus endocrine therapy (ET) after breast-conserving surgery., Patients and Methods: We queried our institutional breast cancer database for the following patients: age > 65 years, stage T1-T2N0, HR(+), and treatment with breast-conserving surgery, including adjuvant RT. The χ(2) analysis identified significant baseline differences between the groups. Cox proportional hazard methods identified predictors of endpoints on multivariate analysis. Kaplan-Meier estimates of survival were compared using the log-rank test., Results: A total of 504 patients were identified, 311 had undergone RT plus ET (62%) and 193, RT alone (38%). The median follow-up time was 88 months. The RT-alone group versus RT plus ET group had different median age (72 vs.71 years, P < .001), different median tumor size (1 vs. 1.3 cm, P < .001), lower grade (40% vs. 29%, P = .05), and fewer close or positive margins (11% vs. 19%, P = .01). The adherence rate to prescribed ET was 70%. Tumor size predicted an increased risk of distant metastasis (DM) (hazard ratio, 1.96; 95% confidence interval [CI], 1.23-3.13) and worse disease-free survival (DFS) (hazard ratio, 1.86; 95% CI, 1.22-2.86). ET nonadherence versus adherence predicted for risk of DM (hazard ratio, 5.03; 95% CI, 1.98-12.66) and DFS (HR, 4.24; 95% CI, 1.9-10.3). Of the women with DM, 83.8% had tumors > 1 cm in size., Conclusion: ET nonadherence and tumor size > 1 cm predicted an increased risk of DM and worse DFS, favoring the addition of ET in this group. However, RT alone for women with tumors less than or equal to 1 cm may be appropriate., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Adrenergic signaling results from the effects of the catecholamines epinephrine and norepinephrine, on alpha- and beta-adrenergic receptors. In breast cancer, preclinical models suggest that this pathway may influence breast cancer progression through 1) increasing tumor cell survival after exposure to chemotherapeutic agents; 2) increasing breast cancer cell proliferation; and 3) altering the tumor microenvironment in angiogenesis and the inflammatory response. Epidemiologic data have suggested a correlation between drugs that indirectly affect the adrenergic pathway and breast cancer incidence. In addition, there is retrospective evidence suggesting that the use of β-adrenergic blockers in early stage breast cancer patients correlates with an increased time to recurrence. Here we review evidence from both pre-clinical models and epidemiological studies that have examined the question of whether adrenergic signaling may modify breast cancer biology.