Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer.

BACKGROUND: Inavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex (encoded by PIK3CA) that also promotes the degradation of mutated p110α. Inavolisib plus palbociclib-fulvestrant has shown synergistic activity in preclinical models and promising antitumor activity in early-phase trials. METHODS: In a phase 3, double-blind, randomized trial, we compared first-line inavolisib (at an oral dose of 9 mg once daily) plus palbociclib-fulvestrant (inavolisib group) with placebo plus palbociclib-fulvestrant (placebo group) in patients with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after the completion of adjuvant endocrine therapy. The primary end point was progression-free survival as assessed by the investigator. RESULTS: A total of 161 patients were assigned to the inavolisib group and 164 to the placebo group; the median follow-up was 21.3 months and 21.5 months, respectively. The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI, 5.6 to 9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32 to 0.59; P<0.001). An objective response occurred in 58.4% of the patients in the inavolisib group and in 25.0% of those in the placebo group. The incidence of grade 3 or 4 neutropenia was 80.2% in the inavolisib group and 78.4% in the placebo group; grade 3 or 4 hyperglycemia, 5.6% and 0%, respectively; grade 3 or 4 stomatitis or mucosal inflammation, 5.6% and 0%; and grade 3 or 4 diarrhea, 3.7% and 0%. No grade 3 or 4 rash was observed. Discontinuation of any trial agent because of adverse events occurred in 6.8% of the patients in the inavolisib group and in 0.6% of those in the placebo group. CONCLUSIONS: In patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).

Risk of male breast cancer after Hodgkin lymphoma.

Female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy have a strongly increased risk of breast cancer (BC), but the treatment-specific BC risk in male survivors of HL has not been evaluated. We assessed BC risk in a cohort of 3077 male survivors of 5-year HL treated at age ≤51 years in 20 Dutch hospitals between 1965 and 2013. We estimated standardized incidence ratios (SIRs), absolute excess risks per 10 000 person-years, and cumulative BC incidences. After a 20-year median follow-up, we observed 8 cases of male with BC. Male survivors of HL experienced a 23-fold (95% confidence interval [CI], 10.1-46.0) increased BC risk compared with the general population, representing 1.6 (95% CI, 0.7-3.3) excess BC incidences per 10 000 person-years. The 20- and 40-year cumulative BC incidences after HL treatment were 0.1% (95% CI, 0.02-0.3) and 0.7% (95% CI, 0.3-1.4), respectively. Treatment with chest radiotherapy without alkylating chemotherapy yielded a strongly increased SIR (20.7; 95% CI, 2.5-74.8), which was not significantly different for chest radiotherapy and alkylating chemotherapy (41.1; 95% CI, 13.4-96.0). Males treated with chest radiotherapy and anthracyclines had an SIR of 48.1 (95% CI, 13.1-123.1). Two patients died from BC (median follow-up, 4.7 years). To ensure early diagnosis and treatment, clinicians should be alert to BC symptoms in male survivors of HL.

Pathogenic variant detection rate varies considerably in male breast cancer families and sporadic cases: minimal additional contribution beyond BRCA2, BRCA1 and CHEK2.

BACKGROUND: Male breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying component of high and moderate risk gene pathogenic variants (PVs) than female breast cancer, particularly in BRCA2. However, most studies only report overall detection rates without assessing detailed family history. METHODS: We reviewed germline testing in 204 families including at least one MBC for BRCA1, BRCA2, CHEK2 c.1100DelC and an extended panel in 93 of these families. Individuals had MBC (n=118), female breast cancer (FBC)(n=80), ovarian cancer (n=3) or prostate cancer-(n=3). Prior probability of having a BRCA1/2 PV was assessed using the Manchester Scoring System (MSS). RESULTS: In the 204 families, BRCA2 was the major contributor, with 51 (25%) having PVs, followed by BRCA1 and CHEK2, with five each (2.45%) but no additional PVs identified, including in families with high genetic likelihood on MSS. Detection rates were 85.7% (12/14) in MSS ≥40 and 65.5% with MSS 30-39 but only 12.8% (6/47) for sporadic breast cancer. PV rates were low and divided equally between BRCA1/2 and CHEK2. CONCLUSION: As expected, BRCA2 PVs predominate in MBC families with rates 10-fold those in CHEK2 and BRCA1. The MSS is an effective tool in assessing the likelihood of BRCA1/2 PVs.

Exploring the One Health Paradigm in Male Breast Cancer.

How cancer patterns in humans compare to those of other species remains largely unknown and there is an even bigger knowledge gap for rare cancers like male breast cancer. One Health is a convergence of human and animal healthcare that encourages cross-pollination of medical research uniting human and veterinary medicine. Recognising that breast cancer occurs spontaneously in other male species (e.g. primates, canines, felines), and knowing that no laboratory models exist for male breast cancer, which limits our ability to perform functional studies, we explored the feasibility of applying One Health to breast cancer in men by conducting a narrative review of the topic. Spontaneous development of breast cancer was reported in captive male primates and in companion canines and felines. Some parallels in tumour biology of human male breast cancer with canines and primates were found. The age distribution, pattern of biomarker expression and metastasis were similar, with mammary tumours typically detected after two-thirds of average lifespan. However, instances of triple negative and inflammatory breast cancer, which are rarely observed in human male breast cancer, were found in canines and histological classification was inconsistent between species. These disparities need redressing to enable full exploration of the One Health paradigm in rare cancers.

Genomic profiling and comparative analysis of male versus female metastatic breast cancer across subtypes.

BACKGROUND: Male breast cancer (MaBC) has limited data on genomic alterations. We aimed to comprehensively describe and compare MaBC's genomics with female breast cancer's (FBC) across subtypes. METHODS: Using genomic data from Foundation Medicine, we categorized 253 MaBC into estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 210), ER-positive/HER2-positive (n = 22) and triple-negative (n = 20). One ER-negative/HER2-positive case was excluded due to n-of-1. The genomics of the final MaBC cohort (n = 252) were compared to a FBC cohort (n = 2708) stratified by molecular subtype, with adjusted p-values. In the overall MaBC and FBC cohorts, we compared mutational prevalence in cancer susceptibility genes (CSG) (ATM/BRCA1/BRCA2/CHEK2/PALB2). RESULTS: Comparing ER-positive/HER2-negative cases, MaBc had increased alterations in GATA3 (26.2% vs. 15.9%, p = 0.005), BRCA2 (13.8% vs. 5.3%, p < 0.001), MDM2 (13.3% vs. 6.14%, p = 0.004) and CDK4 (7.1% vs. 1.8%, p < 0.001); and decreased frequency of TP53 (11.0% vs. 42.6%, p < 0.001) and ESR1 mutations (5.7% vs. 14.6%, p < 0.001). Comparing ER-positive/HER2-positive cases, MaBC had increased short variants in ERBB2 (22.7% vs. 0.6%, p = 0.002), GATA3 (36.3% vs. 6.2%, p = 0.004), and MDM2 (36.3% vs. 4.9%, p = 0.002); decreased frequency of TP53 alterations was seen in MaBC versus FBC (9.1% vs. 61.7%, p < 0.001). Within triple-negative cases, MaBC had decreased alterations in TP53 compared to FBC (25.0% vs. 84.4%, p < 0.001). MaBC had higher frequency of CSG variants than FBC (22.6% vs. 14.6%, p < 0.05), with increased BRCA mutations in MaBC (14.6% vs. 9.1%, p < 0.05). CONCLUSIONS: Although MaBC and FBC share some common alterations, our study revealed several important differences relevant to tumor biology and implications for targeted therapies.

Treatment and Prognosis of Male Breast Cancer: A Multicentric, Retrospective Study Over 11 Years in the Czech Republic.

PURPOSE: Male breast cancer (MBC) is a rare, but increasingly common disease, and lacks prospective studies. Collaborative efforts are needed to understand and address MBC, including its prognosis, in different countries. METHODS: We retrospectively reviewed the clinical, histopathological, and molecular-genetic characteristics, treatments, and survival outcomes of MBC diagnosed between 2007 and 2017 in the Czech Republic. Prognostic factors of overall survival (OS), recurrence-free interval (RFi), and breast cancer-specific mortality (BCSM) were analyzed and indirectly compared to international data. RESULTS: We analyzed 256 patients with MBC (median age 66 years), including 12% with de novo metastatic (M1). Of 201 non-metastatic (M0) patients, 6% were <40 years old, 29% had stage I, 55% were cN0, and 54% underwent genetic testing. Overall, 97% of tumors had estrogen receptor expression ≥10%, 61% had high Ki67 index, 40% were high-grade (G3), and 68% were luminal B-like (HER2-negative). Systemic therapies included endocrine therapy (90%) and chemotherapy (53%). Few (5%) patients discontinued adjuvant endocrine therapy for reasons other than disease relapse or death. Patients treated with aromatase inhibitors alone had significantly shorter RFi (P < .001). OS, RFi, and BCSM were associated with disease stage, T stage, N stage, progesterone receptor expression, grade, and Ki67 index. Median OS reached 122 and 42 months in M0 and de novo M1 patients, respectively. CONCLUSION: Due to the rarity of MBC, this study highlights important findings from real clinical practice. Although the number of patients with MBC with unfavorable features was higher in this Czech dataset than in international studies, the prognosis remains consistent with real-world evidence.

Influence of tumour grade on disease survival in male breast cancer patients: a systematic review.

PURPOSE: Histological grading of tumours is a well-established biomarker used to guide treatment in female breast cancer. However, its significance in male breast cancer remains unclear. This systematic review investigates the prognostic significance of tumour grade in relation to breast cancer-specific survival (BCSS) in male breast cancer patients undergoing surgery. METHODS: MEDLINE, PUBMED Central and EMBASE databases were searched to identify randomised trials and observational studies related to male breast neoplasms, tumour grading, recurrence, and survival. RESULTS: A total of fifteen observational type studies were included in the review. A significant association between tumour grade and BCSS was reported in a majority of studies. This association was most evident with regard to high-grade (grade III) compared to low grade (grade I) tumours, with a significant relationship in 4 out of 4 studies. For intermediate-grade II tumours an association was demonstrated in a minority of studies. CONCLUSIONS: This study confirms an association between high-grade male breast cancers and poorer disease-specific survival, however, the significance of intermediate-grade tumours remains unclear. Further research is required to investigate the biology of male breast cancer in relation to histological grade and optimally define intermediate-grade disease.

Male breast cancer: a multicenter study to provide a guide for proper management.

INTRODUCTION: To offer an extensive retrospective experience on the management of male breast cancer. METHODS: A multicenter retrospective observational cohort study was conducted, including male patients diagnosed with breast cancer (invasive or in situ) in 12 Italian breast units from January 1975 to December 2019. Patients aged 18 years or older were assessed for eligibility. Exclusion criteria were metastatic cancer at diagnosis, previous cancer(s), received neoadjuvant treatment, incomplete data on (neo) adjuvant treatment(s), and/or follow-up data. Data on radiological examinations, demographic characteristics, risk factors, histological features, receptor status, treatments, and follow-up were collected. RESULTS: In a series of 671 male patients with breast cancer assessed for eligibility, 403 (28 in situ and 375 invasive neoplasms) were included in the study. All included patients underwent surgery. The median age at surgery was 63.8 years (IQR 56.1-72.1). In 68% of cases, patients underwent echography, and in 55.1%, a mammography. Most patients were ER and PR positive (63.8%), HER2 negative (80.4%), with high (≥ 20%) Ki67 values (61.3%), and luminal B subtype (51.1%). The 10-year overall survival was 73.6% (95% CI 67.0-79.1) for invasive breast cancer and 90% (95% CI 65.6-97.4) for in situ breast cancer. In patients with invasive breast cancer, at univariable analysis, having a G3 tumor (vs. G1), pT2/3/4 (vs. pT1), pN2/3 (vs. pN0), luminal B subtype with Ki67 ≥ 20% (vs. Luminal A), were significantly associated with a higher risk of death. In multivariable analyses, pT2/3/4 (vs. pT1) remained significantly associated with a higher risk of death (HR 3.14, 95% CI 1.83-5.39), and having a HER2 positive or a triple-negative subtype (vs. Luminal A) was also significantly associated with a higher risk of mortality (HR 4.76, 95% CI 1.26-18.1). CONCLUSION: Male breast cancer is a rare disease, the better understanding of which is necessary for a more effective diagnostic and therapeutic approach.

Whole-Genome Sequencing Analysis of Male Breast Cancer Unveils Novel Structural Events and Potential Therapeutic Targets.

The molecular characterization of male breast cancer (MaBC) has received limited attention in research, mostly because of its low incidence rate, accounting for only 0.5% to 1% of all reported cases of breast cancer each year. Managing MaBC presents significant challenges, with most treatment protocols being adapted from those developed for female breast cancer. Utilizing whole-genome sequencing (WGS) and state-of-the-art analyses, the genomic features of 10 MaBC cases (n = 10) were delineated and correlated with clinical and histopathologic characteristics. Using fluorescence in situ hybridization, an additional cohort of 18 patients was interrogated to supplement WGS findings. The genomic landscape of MaBC uncovered significant genetic alterations that could influence diagnosis and treatment. We found common somatic mutations in key driver genes, such as FAT1, GATA3, SMARCA4, and ARID2. Our study also mapped out structural variants that impact cancer-associated genes, such as ARID1A, ESR1, GATA3, NTRK1, and NF1. Using a WGS-based classifier, homologous recombination deficiency (HRD) was identified in 2 cases, both presenting with deleterious variants in BRCA2. Noteworthy was the observation of FGFR1 amplification in 21% of cases. Altogether, we identified at least 1 potential therapeutic target in 8 of the 10 cases, including high tumor mutational burden, FGFR1 amplification, and HRD. Our study is the first WGS characterization of MaBC, which uncovered potentially relevant variants, including structural events in cancer genes, HRD signatures, and germline pathogenic mutations. Our results demonstrate unique genetic markers and potential treatment targets in MaBC, thereby underlining the necessity of tailoring treatment strategies for this understudied patient population. These WGS-based findings add to the growing knowledge of MaBC genomics and highlight the need to expand research on this type of cancer.

Implementation of Choosing Wisely® Recommendations for Lymph Node Surgery in Male Breast Cancer.

BACKGROUND: The Choosing Wisely® (CW) campaign recommended de-implementation of surgical management of axillary nodes in specified patients. This study aimed to assess trends in the application of CW guidelines for lymph node (LN) surgery in males with breast cancer. METHODS: The National Cancer Database was queried for males diagnosed with breast cancer from 2017 to 2020. Patients were categorized into two cohorts based on CW criteria. Cohort 1 included all T1-2, clinically node-negative patients who underwent breast-conserving therapy and with ≤ 2 positive nodes, and Cohort 2 included all T1-2, node-negative, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative patients aged ≥ 70 years. In Cohort 1, patients who underwent sentinel LN biopsy (SLNB) alone were compared with axillary LN dissection (ALND) or no LN surgery, while in Cohort 2, patients who underwent LN surgery were compared with those with no LN surgery. RESULTS: Of 617 patients who met the criteria for Cohort 1, 73.1% underwent SLNB alone compared with ALND (11.8%) or no LN surgery (15.1%). Those who received SLNB alone were younger (65 vs. 68 vs. 73 years; p < 0.001). The annual proportion of males who underwent SLNB alone remained stable from 2017 to 2020. Overall, 1565 patients met the criteria for Cohort 2, and 84.9% received LN surgery. LN surgery was omitted in older patients (81 vs. 77; p < 0.001). The proportion of elderly males with early-stage breast cancer who underwent LN surgery increased from 2017 to 2020. CONCLUSION: This study demonstrates that CW recommendations are not being routinely applied to males. These findings reinforce the need for additional studies and subsequent recommendations for optimal application of axillary surgery de-implementation for males diagnosed with breast cancer.

Experiences and perceptions of men following breast cancer diagnosis: a mixed method systematic review.

BACKGROUND: Men with breast cancer experience unique physical and emotional challenges. However, a thorough understanding of these experiences including the psychosocial effects and supportive care needs have received less attention. In some settings, men with breast cancer experience stigma within the healthcare system and their care needs are not prioritised. This influences the level of professional support offered, consequently worsening their health and well-being outcomes. This review explored the variabilities in the experiences and treatment modalities of male breast cancer (MBC) across different contexts. METHODS: All primary study designs including qualitative, quantitative, and mixed methods studies that reported on the experiences, treatment approaches and outcomes of MBC were included in this systematic review. Six databases (Embase, Medline, PsycINFO, Global Health, CINAHL and Web of Science) were searched for articles from January 2000 to September 2023. A results-based convergence synthesis was used for data analysis and reported using PRISMA guidelines. RESULTS: Of the studies screened (n = 29,687), forty-four fulfilled the predetermined criteria and were included. Our findings relating to the experiences and treatment approaches of MBC are broadly themed into three parts. Theme 1-Navigating through a threat to masculinity: describes how males experienced the illness reflecting on detection, diagnosis, coming to terms with breast cancer, and disclosure. Theme 2- Navigating through treatment: captures the experiences of undergoing breast cancer treatment/ management following their diagnosis. Theme 3-Coping and support systems: describes how MBC patients coped with the disease, treatment process, aftercare/rehabilitative care, and the available support structures. CONCLUSIONS: Men experience a myriad of issues following a breast cancer diagnosis, especially with their masculinity. Awareness creation efforts of MBC among the public and healthcare practitioners are urgently required, which could change the perception of men in promoting early diagnosis, adherence to treatments, post-treatment monitoring, oncological results and a better quality of life. Considerations for training, education and development of specialised guidelines for healthcare practitioners on MBC would provide the necessary knowledge and skills to enhance their practice through the adoption of person-centred and male-specific care strategies. Professional care intervention and support for MBC should not end after the diagnosis phase but should extend to the entire treatment continuum and aftercare including future research focusing on MBC specific clinical trials. TRIAL REGISTRATION: PROSPERO Registration No. CRD42021228778.

Racial Differences in Germline Genetic Testing Completion Among Males With Pancreatic, Breast, or Metastatic Prostate Cancers.

BACKGROUND: Germline genetic testing is a vital component of guideline-recommended cancer care for males with pancreatic, breast, or metastatic prostate cancers. We sought to determine whether there were racial disparities in germline genetic testing completion in this population. PATIENTS AND METHODS: This retrospective cohort study included non-Hispanic White and Black males with incident pancreatic, breast, or metastatic prostate cancers between January 1, 2019, and September 30, 2021. Two nationwide cohorts were examined: (1) commercially insured individuals in an administrative claims database, and (2) Veterans receiving care in the Veterans Health Administration. One-year germline genetic testing rates were estimated by using Kaplan-Meier methods. Cox proportional hazards regression was used to test the association between race and genetic testing completion. Causal mediation analyses were performed to investigate whether socioeconomic variables contributed to associations between race and germline testing. RESULTS: Our cohort consisted of 7,894 males (5,142 commercially insured; 2,752 Veterans). One-year testing rates were 18.0% (95% CI, 16.8%-19.2%) in commercially insured individuals and 14.2% (95% CI, 11.5%-15.0%) in Veterans. Black race was associated with a lower hazard of testing among commercially insured individuals (adjusted hazard ratio [aHR], 0.73; 95% CI, 0.58-0.91; P=.005) but not among Veterans (aHR, 0.99; 95% CI, 0.75-1.32; P=.960). In commercially insured individuals, income (aHR, 0.90; 95% CI, 0.86-0.96) and net worth (aHR, 0.92; 95% CI, 0.86-0.98) mediated racial disparities, whereas education (aHR, 0.98; 95% CI, 0.94-1.01) did not. CONCLUSIONS: Overall rates of guideline-recommended genetic testing are low in males with pancreatic, breast, or metastatic prostate cancers. Racial disparities in genetic testing among males exist in a commercially insured population, mediated by net worth and household income; these disparities are not seen in the equal-access Veterans Health Administration. Alleviating financial and access barriers may mitigate racial disparities in genetic testing.

Establishment of Prognostic Nomogram for Male Breast Cancer Patients: A Surveillance, Epidemiology and End Results Database Analysis.

BACKGROUND: Male breast cancer (MBC) represents a rare subtype of breast cancer, with limited prognostic factor studies available. The purpose of this research was to develop a unique nomogram for predicting MBC patient overall survival (OS) and breast cancer-specific survival (BCSS). METHODS: From 2010 to 2020, clinical characteristics of male breast cancer patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Following univariate and multivariate analyses, nomograms for OS and BCSS were created. Kaplan-Meier plots were further generated to illustrate the relationship between independent risk variables and survival. The nomogram's ability to discriminate was measured by employing the area under a time-dependent receiver operating characteristic curve (AUC) and calibration curves. Additionally, when the nomogram was used to direct clinical practice, we also used decision curve analysis (DCA) to evaluate the clinical usefulness and net clinical benefits. RESULTS: A total of 2143 patients were included in this research. Univariate and multivariate analysis showed that age, grade, surgery, chemotherapy status, brain metastasis status, subtype, marital status, race, and AJCC-T, AJCC-N, and AJCC-M stages were significantly correlated with OS. Lung metastasis, age, marital status, grade, surgery, and AJCC-T, AJCC-N, and AJCC-M stages were significantly correlated with BCSS. By comprising these variables, a predictive nomogram was constructed in the SEER cohort. Then, it could be validated well in the validation cohort by receiver operating characteristics (ROCs) curve and calibration plot. Furthermore, the nomogram demonstrated better decision curve analysis (DCA) results, indicating the ability to forecast survival probability with greater accuracy. CONCLUSION: We created and validated a unique nomogram that can assist clinicians in identifying MBC patients at high risk and forecasting their OS/BCSS.

Management of Male Patients With Occult Breast Cancer: Analysis of the National Cancer Database.

INTRODUCTION: Occult breast cancer (OBC) consists of <0.1% of breast cancer cases in the United States. Male occult breast cancer (mOBC) has not been well-studied outside of case reports, and management is largely based on female OBC (fOBC) studies. We aim to examine the prevalence of mOBC among those in the National Cancer Database with breast cancer and describe treatment modalities received by mOBC compared to fOBC. METHODS: The National Cancer Database was queried for patients with OBC from 2004 to 2018. Chi-Square test and Fisher's exact tests compared patient, clinical, and facility characteristics by sex. Treatment modalities [systemic therapy, radiation therapy, axillary lymph node dissection, modified radical mastectomy (MRM)] were compared. A subgroup analysis examined pathologic upstaging in patients who underwent MRM. RESULTS: Of 23,374 male patients with breast cancer, 0.13% were identified to have mOBC [versus 0.09% in fOBC]. cN2/N3 disease was significantly more prevalent in the mOBC cohort (61.3%) than in the fOBC cohort (30.7%, P < 0.001). Receipt of axillary lymph node dissection or MRM was not significantly different by sex. Male OBC (mOBC) patients were less likely to receive trimodality treatment than fOBC patients. In patients who underwent MRM, more mOBC patients [75%] were pathologically upstaged as T+ after mastectomy than fOBC patients [30%, P < 0.001], questioning the adequacy of diagnostic workup for mOBC compared to fOBC. CONCLUSIONS: This review confirms mOBC as an extremely rare disease. Multimodal treatments have been highly utilized to optimize care in this patient population. Further investigation is warranted to examine the survival benefit of treatment regimens for mOBC.

Imaging the Male Breast: Gynecomastia, Male Breast Cancer, and Beyond.

The number of men undergoing breast imaging has increased in recent years, according to some reports. Most male breast concerns are related to benign causes, most commonly gynecomastia. The range of abnormalities typically encountered in the male breast is less broad than that encountered in women, given that lobule formation rarely occurs in men. Other benign causes of male breast palpable abnormalities with characteristic imaging findings include lipomas, sebaceous or epidermal inclusion cysts, and intramammary lymph nodes. Male breast cancer (MBC) is rare, representing up to 1% of breast cancer cases, but some data indicate that its incidence is increasing. MBC demonstrates some clinical features that overlap with those of gynecomastia, including a propensity for the subareolar breast. Men with breast cancer tend to present at a later stage than do women. MBC typically has similar imaging features to those of female breast cancer, often characterized by an irregular mass that may have associated calcifications. Occasionally, however, MBC has a benign-appearing imaging phenotype, with an oval shape and circumscribed margins, and therefore most solid breast masses in men require tissue diagnosis. Histopathologic evaluation may alternatively reveal other benign breast masses found in men, including papillomas, myofibroblastomas, and hemangiomas. Radiologists must be familiar with the breadth of male breast abnormalities to meet the rising challenge of caring for these patients. ©RSNA, 2024 Supplemental material is available for this article.

Male Breast Cancer: a Review on Diagnosis, Treatment, and Survivorship.

PURPOSE OF REVIEW: Male breast cancer is a relatively uncommon and rare disease that is often managed based on evidence adopted from trials pertaining to female breast cancer due to low accrual rates or exclusion of males. This is despite the known differences in the biology and epidemiology of this condition. This review provides an update regarding the management and surveillance of male breast cancer. RECENT FINDINGS: Men with breast cancer tend to undergo more extensive surgery in the breast and axilla. The outcomes of male breast cancer compared to a similar subtype of female breast cancer appear worse when matched for stage. Systemic therapies remain predominantly based on recommendations for female breast cancer, although tamoxifen is the more optimal endocrine therapy for men than women. Surveillance with mammograms is recommended for patients harboring a breast cancer susceptibility gene but is otherwise not advised for men who have undergone a mastectomy. Notably, the role of other imaging modalities, including ultrasound and magnetic resonance imaging, is minimal. Although the focus on survivorship care among men is low, it is abundantly clear that this is a stigmatizing diagnosis for men, and they suffer from long-term physical and psychological sequelae following a diagnosis and treatment of breast cancer. In summary, providing more gender-inclusive care and advocating for increased representation of men in prospective breast cancer studies and clinical trials may help improve outcomes and provide enhanced support for this population.

The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

Adjuvant chemotherapy and survival in males aged 70 years or older with breast cancer: a population-based retrospective study.

BACKGROUND: Male breast cancer constitutes a minority of breast cancer diagnoses, yet its incidence has been on the rise in recent decades. However, elderly male breast cancer patients have been inadequately represented in clinical trials, posing challenges in treatment decisions. This study seeks to clarify the efficacy of chemotherapy in this demographic and identify the population most likely to benefit from such intervention. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 1900 male breast cancer patients aged 70 years or older. Among them, 1652 were categorized in the no-chemotherapy group, while 248 were in the chemotherapy group. A multifactorial logistic regression model was employed to investigate the determinants influencing the administration of chemotherapy in elderly male breast cancer patients. Additionally, the multivariate Cox proportional hazards regression model was applied to identify factors associated with outcomes, with overall survival (OS) as the primary endpoint. RESULTS: Multivariate logistic regression analysis revealed that grade, tumor size, and nodal status were robust predictors for elderly male breast cancer patients receiving chemotherapy. Furthermore, the multivariate analysis demonstrated that chemotherapy conferred benefits compared to the no-chemotherapy group (HR = 0.822, 95% CI: 0.682-0.991, p = 0.040). Stratified analyses indicated that individuals with N+, poorly/undifferentiated grade, and stage II/III disease could derive benefits from chemotherapy. Upon further investigation of progesterone receptor (PR) positive patients, it was found that only stage III patients experienced significant benefits from chemotherapy (HR = 0.571, 95% CI: 0.372-0.875, p = 0.010). Conversely, in PR negative patients, both stage II (HR = 0.201, 95% CI: 0.051-0.792, p = 0.022) and stage III patients (HR = 0.242, 95% CI: 0.060-0.972, p = 0.046) derived benefits from chemotherapy. CONCLUSION: Adjuvant chemotherapy may benefit certain elderly male breast cancer patients, specifically those with positive lymph node status, poorly/undifferentiated grade, and PR-positive in stage III, as well as PR-negative expression in stage II/III. Given favorable physical tolerance, it is advisable not to hastily dismiss chemotherapy for these elderly male breast cancer patients.

Melanoma Mimicker: Pigmented Mammary Paget Disease in a Man.

ABSTRACT: Male breast cancer comprises less than 1% of all breast cancer cases. Mammary Paget disease (MPD) represents a subset of breast cancer that presents with skin changes of the nipple and areola, and is frequently misdiagnosed clinically due to similarities with other disease states, leading to an average delay in diagnosis of 1 month to 2 years. Pigmented mammary Paget disease (PMPD) is an uncommon variant of MPD that clinically and histologically resembles malignant melanoma. Due to variable immunohistochemical staining patterns, analysis can be challenging and often requires interpretation of panels for accurate diagnosis. We present a rare case of PMPD in a male, originally diagnosed both clinically and histologically as malignant melanoma, to highlight the diagnostic challenges that this entity presents, and to review staining patterns which may be useful in its diagnosis.

Breast cancer mortality in Chinese women and men from 1990 to 2019: Analysis of trends in risk factors.

OBJECTIVE: This study aimed to examine the relative risk of risk factor in male and female breast cancer (BC) deaths in China and analyzed the changing trends in BC mortality rates from 1990 to 2019. METHODS: Open data from the Global Burden of Disease database from 1990 to 2019 were analyzed to assess the number of BC deaths and age-standardized mortality rates (ASMR) in China. The age-period-cohort model was employed to study age effects, period effects, cohort effects, as well as local drift and net drift of the data, determining the impact of changing risk factors on crude mortality rates and ASMR of BC. RESULTS: In 2019, the number of BC deaths across all age groups in China increased by 130.38% compared to 1990, with an increase of 125.68% in females and 648.80% in males. The ASMR for BC and male BC increased in 2019, while female BC ASMR declined. Overall, alcohol consumption and smoking as risk factors contributed to increased mortality rates of BC with advancing age. Over the entire study period, the net drift of alcohol consumption in females for BC was 0.06% (95% confidence interval [CI]: -0.24% to 0.36%), while for smoking it was -0.64% (95% CI: -0.83% to -0.45%). For males, the net drift of alcohol consumption for BC was 6.75% (95% CI: 5.55% to 7.96%), and for smoking, it was 6.09% (95% CI: 2.66% to 9.64%). CONCLUSION: Hence, improving awareness of BC-related risk factors and implementing prevention strategies are necessary to alleviate future BC burdens.