Male ductal carcinoma in situ: diagnosis and management of a rare disease in men.

Ductal carcinoma in situ is very rare in male patients, accounting for approximately 5%-7% of all male breast cancers. We present a case of a man in his early 70s who presented with bloody nipple discharge and gynaecomastia and was subsequently diagnosed with ductal carcinoma in situ (DCIS). We discuss his management with surgical resection and the consideration of adjuvant treatment. We also review the existing literature on the presentation, diagnosis and management of DCIS in men.

Evaluation of Faculty Parental Leave Policies at Medical Schools Ranked by US News & World Report in 2020.

Importance: Physician parents, particularly women, are more likely to experience burnout, poor family-career balance, adverse maternal and fetal outcomes, and stigmatization compared with nonparent colleagues. Because many physicians delay child-rearing due to the rigorous demands of medical training, favorable parental leave policies for faculty physicians are crucial to prevent physician workforce attrition. Objective: To evaluate paid and unpaid parental leave policies at medical schools ranked by US News & World Report in 2020 and identify factors associated with leave policies. Design, Setting, and Participants: This cross-sectional national study was performed at US medical schools reviewed from December 1, 2019, through May 31, 2020, and February 1 through March 31, 2021, due to the COVID-19 pandemic. All medical schools ranked by US News & World Report in 2020 were included. Main Outcomes and Measures: The primary outcome was the number of weeks of paid and unpaid leave for birth, nonbirth, adoption, and foster care physician parents. Institutional policies for the number of weeks of leave and requirements to use vacation, sick, or disability leave were characterized. Institutional factors were evaluated for association with the duration of paid parental leave using χ2 tests. Results: Among the 90 ranked medical schools, 87 had available data. Sixty-three medical schools (72.4%) had some paid leave for birth mothers, but only 13 (14.9%) offered 12 weeks of fully paid leave. While 11 medical schools (12.6%) offered 12 weeks of full paid leave for nonbirth parents, 38 (43.7%) had no paid leave for nonbirth parents. Adoptive and foster parents had no paid leave in 35 (40.2%) and 65 (74.7%) medical schools, respectively. Median paid parental leave was 4 (IQR, 0-8) weeks for birth parents, 4 (IQR, 0-6) weeks for adoptive parents, 3 (IQR, 0-6) weeks for nonbirth parents, and 0 (IQR, 0-1) weeks for foster parents. About one-third of medical schools required birth mothers to use vacation (29 [33.3%]), sick leave (31 [35.6%]), or short-term disability (9 [10.3%]). Among institutional characteristics, higher ranking (top vs bottom quartile: 30.4% vs 4.0%; P = .03) and private designation (private vs public, 23.5% vs 9.4%; P < .001) was associated with a higher rate of 12 weeks of paid leave for birth mothers. Conclusions and Relevance: In this cross-sectional national study of medical schools ranked by US News & World Report in 2020, many physician faculty receive no or very limited paid parental leave. The lack of paid parental leave was associated with higher rates of physician burnout and work-life integration dissatisfaction and may further perpetuate sex, racial and ethnic, and socioeconomic disparities in academic medicine.

Concordance of breast cancer biomarker testing in core needle biopsy and surgical specimens: A single institution experience.

BACKGROUND: Accurate diagnostic biomarker testing is crucial to treatment decisions in breast cancer. Biomarker testing is performed on core needle biopsies (CNB) and is often repeated in the surgical specimen (SS) after resection. As differences between CNB and SS testing may alter treatment decisions, we evaluated concordance between CNB and SS as well as associated changes in treatment and clinical outcomes. METHODS: We performed a retrospective analysis of breast cancer patients at our institution between January 2010 and May 2020. Concordance between CNB and SS was assessed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Survival in patients, including recurrence, metastatic recurrence, and death, were assessed using chi-squared likelihood ratio. RESULTS: In total, 961 patients met eligibility criteria. Concordance, minor discordance, total concordance (concordance plus minor discordance), and major discordance between CNB and SS were reported for ER (87.7%, 9.2%, 90.8%, and 2.9%), PR (58.1%, 29.1%, 87.2%, and 12.8%), and HER2 IHC (52.5%, 20.9%, 73.4%, 26.6%), respectively. HER2 FISH concordance and major discordance were 58.5% and 1.2%, respectively. Of major discordance, ER (48.2%, p < 0.001) and HER2 FISH (50.0%) led to more management changes than HER2 IHC (2.4%, p = 0.04) and PR (1.6%, p = 0.10). Patients with ER major discordance had increased risk of death (6.7% concordance vs. 22.2% major discordance, p = 0.004). CONCLUSION: Overall, retesting ER and HER2 was more clinically beneficial than retesting PR. To aid decision-making and minimize healthcare costs, we propose patient-centered guidelines on retesting biomarker profiles.

BRAF V600 Mutation Detection in Plasma Cell-Free DNA: NCCTG N0879 (Alliance).

OBJECTIVE: To evaluate the prognostic significance of detectable circulating cell-free DNA (cfDNA) BRAF V600E/K mutations in patients with advanced melanoma enrolled in a clinical trial without BRAF-targeted therapy. PATIENTS AND METHODS: BRAF V600E/K mutation status was determined on archived tissue and pretreatment stored plasma from 149 patients with unresectable stage IV melanoma who were enrolled between May 5, 2010 and May 2, 2014 in the North Central Cancer Treatment Group/Alliance N0879 randomized phase 2 clinical trial. Results were reported as presence or absence of cfDNA BRAF V600E/K detection of assay vs tissue. Progression-free survival (PFS) and overall survival (OS) were assessed for patients with and without detectable BRAF mutation. RESULTS: In total, 63 of 149 (42.3%) patients had BRAF V600E/K results for tissue and blood, and 20 of 63 (31.7%) patients had tissue-diagnosed mutant BRAF. Of these, 11 of 20 (55.0%) patients had detectable plasma cfDNA BRAF. Among patients with tissue-mutant BRAF V600E/K, PFS and OS were shorter for those with corresponding cfDNA mutations (PFS, 5.8 vs 12.0 months; P=.051; OS, 9.2 vs 27.1 months; P=.054). Our assay demonstrated sensitivity of 55% (95% CI, 0.322 to 0.768), specificity of 97.7% (95% CI, 0.932 to 1.000), positive predictive value of 91.7% (95% CI, 0.760 to 1.000), and negative predictive value of 82.4% (95% CI, 0.719 to 0.928). CONCLUSION: In advanced melanoma, detectable cfDNA BRAF V600E/K mutation is present in about half the patients with stage IV with BRAF-mutant melanoma tumor tissue and appears to confer a poorer prognosis when detectable. Given the poorer prognosis, cfDNA can be used to risk-stratify patients with metastatic melanoma in practice or clinical trials.Trial Registration: clinicaltrials.gov Identifier: NCT00976573.

Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.

Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.

Gestational breast cancer: current challenges in staging and treatment of breast cancer.

Gestational breast cancer (GBC) is the most common form of invasive cancer in pregnancy and has unique challenges in both staging and treatment given the dual goal of appropriate cancer management and minimising the risk of fetal toxicity. A 38-year-old woman with no significant medical history and 21 weeks pregnant presented with a palpable right breast mass. She was diagnosed with human epidermal growth factor receptor 2-positive infiltrating ductal carcinoma with advanced disease. The patient underwent treatment; however, unfortunately, she passed away after developing devastating distant disease recurrence.We highlight both the challenges and current guidelines for management of GBC. Our goal is to discuss the current limitations of GBC management and the necessity of further investigation for safe novel imaging and treatment modalities for pregnant women. It is crucial to increase awareness across multiple subspecialities, as a multidisciplinary team is necessary for proper treatment of GBC.

NCCTG N0879 (Alliance): A randomized phase 2 cooperative group trial of carboplatin, paclitaxel, and bevacizumab ± everolimus for metastatic melanoma.

BACKGROUND: Despite the success of immune checkpoint and targeted therapy, many patients with melanoma ultimately require further treatment. The combination of carboplatin, paclitaxel, and bevacizumab (CPB) has demonstrated promising activity in a single-arm study. In the current study, the authors performed a randomized phase 2 study to confirm efficacy and to determine whether adding everolimus would increase the activity of the combination. METHODS: Through the North Central Cancer Treatment Group, a total of 149 patients with unresectable AJCC 6th edition stage IV melanoma were randomized from May 2010 to May 2014 to either CPB or CPB with everolimus (CPBE). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate, and tolerability. RESULTS: The CPB and CPBE treatment arms were balanced with regard to age (median age: 59 years vs 58 years) and high lactate dehydrogenase (48% vs 51%), but were unbalanced with regard to sex (male sex: 72% vs 55%; P = .03). Overall, there was no difference noted with regard to PFS, with a median PFS of 5.6 months for CPB versus 5.1 months for CPBE (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.81-1.62 [P = .44]), or for OS, with a median OS of 14.5 months for CPB versus 10.8 months for CPBE (HR, 1.16; 95% CI, 0.84-1.84). The confirmed response rate was 13% for CPB and 23% for CPBE (P = .13). Toxicity was higher for CPBE compared with CPB (83% for grade 3 + and 14% for grade 4 + vs 63% for grade 3 + and 11% for grade 4+, respectively) (toxicities were graded using the Cancer Therapy Evaluation Program of the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Common grade 3 + toxicities were neutropenia, leukopenia, and fatigue, which occurred in both treatment arms with comparable frequency. CONCLUSIONS: Both experimental arms demonstrated activity, with a PFS of >5 months. However, the addition of everolimus to CPB failed to improve outcomes, with increased toxicity noted. These findings replicate the moderate antitumor activity of CPB, with future development possibly in combination with targeted or immunotherapy. Cancer 2018;124:537-45. © 2017 American Cancer Society.