CHEK2 is considered to be involved in homologous recombination repair (HRR). Individuals who have germline pathogenic variants (gPVs) in CHEK2 are at increased risk to develop breast cancer and likely other primary cancers. PARP inhibitors (PARPi) have been shown to be effective in the treatment of cancers that present with HRR deficiency-for example, caused by inactivation of BRCA1/2. However, clinical trials have shown little to no efficacy of PARPi in patients with CHEK2 gPVs. Here, we show that both breast and non-breast cancers from individuals who have biallelic gPVs in CHEK2 (germline CHEK2 deficiency) do not present with molecular profiles that fit with HRR deficiency. This finding provides a likely explanation why PARPi therapy is not successful in the treatment of CHEK2-deficient cancers.

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.

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.
CONCLUSIONS: 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.

OBJECTIVE: Randomized clinical trials demonstrate that lumpectomy + hormone therapy (HT) without radiation therapy (RT) yields equivalent survival and acceptable local-regional outcomes in elderly women with early-stage, node-negative, hormone-receptor positive (HR +) breast cancer. Whether these data apply to men with the same inclusion criteria remains unknown.
METHODS: The National Cancer Database was queried for male patients ≥ 65 years with pathologic T1-2N0 (≤ 3 cm) HR + breast cancer treated with breast-conserving surgery with negative margins from 2004 to 2019. Adjuvant treatment was classified as HT alone, RT alone, or HT + RT. Male patients were matched with female patients for OS comparison. Survival analysis was performed using Cox regression and Kaplan - Meier method. Inverse probability of treatment weighting (IPTW) was applied to adjust for confounding.
RESULTS: A total of 523 patients met the inclusion criteria, with 24.4% receiving HT, 16.3% receiving RT, and 59.2% receiving HT + RT. The median follow-up was 6.9 years (IQR: 5.0-9.4 years). IPTW-adjusted 5-yr OS rates in the HT, RT, and HT + RT cohorts were 84.0% (95% CI 77.1-91.5%), 81.1% (95% CI 71.1-92.5%), and 93.0% (95% CI 90.0-96.2%), respectively. On IPTW-adjusted MVA, relative to HT, receipt of HT + RT was associated with improvements in OS (HR: 0.641; p = 0.042). RT alone was not associated with improved OS (HR: 1.264; p = 0.420).
CONCLUSIONS: Among men ≥ 65 years old with T1-2N0 HR + breast cancer, RT alone did not confer an OS benefit over HT alone. Combination of RT + HT demonstrated significant improvements in OS. De-escalation of treatment through omission of either RT or HT at this point should be done with caution.

BACKGROUND: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials.
METHODS: We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC.
RESULTS: We selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group. We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone. Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p < 0.001.
CONCLUSIONS: We confirmed that gender minorities are severely underrepresented among BC registration trials. We observed a lower rate of men in trials envisaging endocrine manipulation or in less contemporary trials. This work sought to urge the scientific community to increase the awareness level towards the issue of gender minorities and to endorse more inclusive criteria in clinical trials.

Male breast cancer (MBC) accounts for approximately 1% of all breast cancers and among these infiltrating lobular carcinomas (ILC) represents only 1-2% of all MBC cases. Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of ILC with only eight cases reported until now in males. Up to 10% of MBC cases have a germline pathogenic variant in a predisposing gene such as BRCA1 and BRCA2 genes. Mutations in PALB2 (partner and localizer of BRCA2) have been reported in men with breast cancer, with a frequency that ranges from 0.8 to 6.4%, but it has never been reported in male ILC. Here, we report a rare and interesting case of an invasive pleomorphic/solid lobular carcinoma, which carries a pathogenic variant in PALB2 gene, and a family history of breast cancer without other well defined risk factors for developing this type of neoplasia. In addition, we review the current literature.

BACKGROUND: Following the positive iDFS and OS results of the phase III clinical trials monarchE, NATALEE and OlympiA, new oral anticancer agents (the CDK4/6 inhibitors abemaciclib, ribociclib as well as the PARP inhibitor olaparib) have recently been introduced into the treatment of high-risk early breast cancer (eBC). However, only few male patients were included in these trials (0.4%, 0.6% and 0.3%, respectively). The objective of this real-world analysis was to determine the proportion of male patients with eBC fulfilling the clinical high-risk criteria of above-mentioned trials.
METHODS: We conducted a data inquiry and analysis with the Cancer Registry of Baden-Württemberg of men with breast cancer diagnosed between January 1, 2015 and December 31, 2021. Men with eBC were identified and the number of patients at clinical high-risk according to the inclusion criteria of monarchE, NATALEE and OlympiA was assessed.
RESULTS: Of 397 men with eBC, 354 (89.1%) had a HR + /Her2- and 4 (1.0%) a triple-negative subtype. 84 patients (21.2%) met the clinical high-risk criteria according to the monarchE, 189 (47.6%) those according to the NATALEE and 50 (12.6%) those according to the OlympiA trial.
CONCLUSIONS: In a large real-world sample, more men with eBC are at clinical high risk according to the inclusion criteria of monarchE, NATALEE and OlympiA than would be expected in women. This is most likely due to more advanced stages at initial diagnosis in men. To evaluate whether CDK4/6 and PARP inhibitors improve prognosis also in men should be the topic of future real- world analyses.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is commonly used in the surgical management of male breast cancer. Contrary to female breast cancer, limited data exist about its performance in male breast cancer. The objective of this systematic review and meta-analysis was to evaluate the SLNB accuracy in male breast cancer.
METHODS: MEDLINE, EMBASE, Web of Science and The Cochrane Library were searched from January 1995 to April 2023 for studies evaluating the SLNB identification rate and false-negative rate in male breast cancer with negative preoperative axillary evaluation and primary surgery. For SLNB false-negative rate, the gold standard was the histology of axillary lymph node dissection (ALDN). Methodological quality was assessed by using the QUADAS-2 tool. Pooled estimates of the SLNB identification rate and false-negative rate were calculated. Heterogeneity of the pooled studies was evaluated using I2 index.
RESULTS: A total of 12 retrospective studies were included. The 12 studies that reported the SLNB identification rate gathered a total of 164 patients; the 5 studies that reported the SLNB false-negative rate gathered a total of 50 patients with a systematic ALND. The pooled estimate of the SLNB identification rate was 99.0%. The SLNB false-negative rates were 0% in the 5 included studies and consequently so as the pooled estimate of the false-negative rate with no heterogeneity.
CONCLUSIONS: SLNB for male breast cancer, following negative preoperative axillary assessment and primary surgery, appears feasible, consistent, and effective. Our research supports conducting immediate SLNB histological evaluation to facilitate prompt ALND in case of positive results.

BACKGROUND: Successful breast cancer outcomes can be jeopardised by adverse events. Understanding and integrating patients\' and doctors\' perspectives into care trajectories could improve patient safety. This study assessed their views on, and experiences of, medical error and patient safety.
METHODS: A cross-sectional, quantitative 20-40 item questionnaire for patients attending Cork University Hospital Cancer Centre and breast cancer doctors in the Republic of Ireland was developed. Domains included demographics, medical error experience, patient safety opinions and concerns.
RESULTS: 184 patients and 116 doctors completed the survey. Of the doctors, 41.4% felt patient safety had deteriorated over the previous five years and 54.3% felt patient safety measures were inadequate compared to 13.0% and 27.7% of patients respectively. Of the 30 patients who experienced medical errors/negligence claims, 18 reported permanent or long-term physical and emotional effects. Forty-two of 48 (87.5%) doctors who experienced medical errors/negligence claims reported emotional health impacts. Almost half of doctors involved in negligence claims considered early retirement. Forty-four patients and 154 doctors didn\'t experience errors but reported their patient safety concerns. Doctors were more concerned about communication and administrative errors, staffing and organisational factors compared to patients. Multiple barriers to error reporting were highlighted.
CONCLUSIONS: This is the first study to assess patients\' and doctors\' patient safety views and medical error/negligence claims experiences in breast cancer care in Ireland. Experience of medical error/negligence claims had long-lasting implications for both groups. Doctors were concerned about a multitude of errors and causative factors. Failure to embed these findings is a missed opportunity to improve safety.

暂无摘要。