Background
Male breast cancer (MBC) is a rare disease for which no randomised controlled trials (RCT) have been conducted to determine optimal surgical management. The available data have been ...reviewed to identify reasonable options and reveal areas in need of investigation.
Methods
All published series on the surgical management of MBC have been reviewed to determine approaches to treatment of the primary, the breast and the axilla together with the psychological sequelae of surgery.
Findings
Mastectomy is still the major surgical offer but a convincing case can be made for the use of neoadjuvant endocrine treatment in order to facilitate breast conserving surgery. Sentinel node biopsy has been successfully used for staging MBC although nomograms for prediction of nodal status are inadequately calibrated. There are psychological sequelae of mastectomy in males and as yet no evidence that the needs of those with MBC are being met.
Conclusions
Collaborative studies are required so that men can participate in meaningful RCTs to provide an evidence-based rational foundation for the surgery of MBC.
Abstract It has become customary to extrapolate from the results of treatment trials for female breastcancer and apply them to males with the disease. In the absence of results from national and ...international randomised trials for male breast cancer (MBC) this appears superficially to be an appropriate response. Closer examination of available data reveals that aspects of the aetiology and treatment of MBC do not fit the simplistic model that men usually have endocrine sensitive tumours which behave like those in postmenopausal women. Most females and males with breast cancer have none of the recognised risk factors, indicating the gaps in our knowledge of the epidemiology of this disease. Several studies have compared epidemiological risk factors for MBC and female breast cancer (FBC) but many have been blighted by small numbers. In comparison with FBC there is a larger proportion of BRCA2 tumours, (occurring in 10% of MBC), and underrepresentation of BRCA1 tumours (found in only 1%), suggesting significant differences in the genetic aetiology of MBC and FBC. Genome-wide association studies in FBC reported single nucleotide polymorphisms (SNPs) in 12 novel independent loci were consistently associated with disease but for MBC 2 SNPs had a significantly increased risk. Molecular profiles of matched cancers in males and females showed a gender-associated modulation of major processes including energy metabolism, regulation of translation, matrix remodelling and immune recruitment. Immunohistochemistry for kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 indicate a significant difference in the immunostaining of tumours from male patients compared with females. MBC is almost always estrogen receptor positive (ER + ve) and so systemic treatment is usually endocrine. With evidence in FBC that aromatase inhibitors are more effective than tamoxifen in the postmenopausal it was seemingly logical that the same would be true for MBC. Results however suggest less efficacy with AIs and an increase in risk of mortality compared to tamoxifen. The overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. These important biological differences point the way to the development of new therapies for MBC based on differences rather than similarities with FBC.
Male breast cancer (MBC) is a rare disease but, as a result of epidemiological collaborations, there is now greater clarity concerning endocrine risk factors. The significant rise in global ...age-standardised mean BMI in men is likely to lead to increases in incidence of maturity-onset diabetes and MBC. The metabolic changes accompanying obesity decrease androgens and sex hormone-binding globulin (SHBG), thereby increasing available oestrogens. The higher rates of MBC in North and Equatorial Africa are largely due to liver damage from endemic bilharziasis and hepatitis B causing elevated oestradiol (E2) levels from hepatic conversion of androgen. Klinefelter’s syndrome (XXY) is associated with a 50-fold increase in incidence of MBC compared with XY males, and this is the most pronounced evidence for testicular malfunction amplifying risk. Delay in presentation means that up to 40% of cases have stage III or stage IV disease at diagnosis. No randomised controlled trials have been reported on endocrine treatment of advanced disease or adjuvant/neoadjuvant therapy following or preceding surgery. Tamoxifen is the most effective endocrine therapy, but side effects can lead to non-compliance in a substantial number of men. Aromatase inhibitors are less effective because they do not inhibit testicular oestrogen production. There is an urgent need for collaborative trials to provide an evidence base for the most effective endocrine and least toxic therapies for men with breast cancer.
Unmet needs of men with breast cancer Fentiman, Ian S.
European journal of surgical oncology,
August 2018, 2018-08-00, 20180801, Letnik:
44, Številka:
8
Journal Article
Recenzirano
Because of the rarity of male breast cancer (MBC) many men are unaware that the disease exists. This leads both to delay in presentation and severe distress after diagnosis concerning loss of ...masculinity and fear about the future. The informational and emotional support needs of men with breast cancer are often not met and many will have undiagnosed and untreated psychological morbidity. There is a pressing need for collaboration and the setting up national networks to improve both the treatment and quality of life of men with breast cancer.
Most adequately powered studies confirm a worse prognosis for males versus matched females with breast cancer. There is in‐stage migration for stage I cancers with a different ratio of tumor/normal ...breast tissue in males. Younger men have a better prognosis, largely the result of increased morbidity in the elderly, exacerbated by smoking, low socioeconomic differences, and ethnic disparity. BRCA2 carriers with MBC have a worse outcome than noncarriers as do men with amplification of EMSY. Men with tumors having a high cytosol level of plasminogen activator inhibitor 1 (PAI‐1) may have more invasive cancers leading to earlier spread and hence a worse outcome. PREDICT+ is a useful prognostic model for MBC and multigene testing enables more specific systemic therapies to be used.
Adjuvant radiotherapy (RT) after a local excision (LE) for ductal carcinoma in situ (DCIS) aims at reduction of the incidence of a local recurrence (LR). We analyzed the long-term risk on developing ...LR and its impact on survival after local treatment for DCIS.
Between 1986 and 1996, 1,010 women with complete LE of DCIS less than 5 cm were randomly assigned to no further treatment (LE group, n = 503) or RT (LE+RT group, n = 507). The median follow-up time was 15.8 years.
Radiotherapy reduced the risk of any LR by 48% (hazard ratio HR, 0.52; 95% CI, 0.40 to 0.68; P < .001). The 15-year LR-free rate was 69% in the LE group, which was increased to 82% in the LE+RT group. The 15-year invasive LR-free rate was 84% in the LE group and 90% in the LE+RT group (HR, 0.61; 95% CI, 0.42 to 0.87). The differences in LR in both arms did not lead to differences in breast cancer-specific survival (BCSS; HR, 1.07; 95% CI, 0.60 to 1.91) or overall survival (OS; HR, 1.02; 95% CI, 0.71 to 1.44). Patients with invasive LR had a significantly worse BCSS (HR, 17.66; 95% CI, 8.86 to 35.18) and OS (HR, 5.17; 95% CI, 3.09 to 8.66) compared with those who did not experience recurrence. A lower overall salvage mastectomy rate after LR was observed in the LE+RT group than in the LE group (13% v 19%, respectively).
At 15 years, almost one in three nonirradiated women developed an LR after LE for DCIS. RT reduced this risk by a factor of 2. Although women who developed an invasive recurrence had worse survival, the long-term prognosis was good and independent of the given treatment.
Risk factors for male breast cancer Fentiman, Ian S
American journal of translational research,
2023, Letnik:
15, Številka:
12
Journal Article
Male breast cancer (MBC) presents problems with identification of high-risk groups. Risk factors include hepatic dysfunction, high ambient working temperature, exposure to exhaust fumes and obesity, ...but none identify a group with a high absolute number of MBC cases. The two significant cohorts are
mutation carriers and individuals with Klinefelter's syndrome (KS), responsible for up to 15% of cases. Since >90% of male tumours are ER+ve, endocrine intervention is logical with the likely agent being tamoxifen. In terms of an acceptable endocrine agent, compliance studies. Compliance studies indicate that men do not tolerate tamoxifen well because of side-effects. Although certain groups with an increased risk of MBC can be identified, the absolute number of cases is small so, at present, a meaningful prevention study is not an option.
Summary Background The EORTC 10801 trial compared breast-conserving therapy (BCT) with modified radical mastectomy (MRM) in patients with tumours 5 cm or smaller and axillary node negative or ...positive disease. Compared with BCT, MRM resulted in better local control, but did not affect overall survival or time to distant metastases. We report 20-year follow-up results. Methods The EORTC 10801 trial was open for accrual between 1980 and 1986 in eight centres in the UK, the Netherlands, Belgium, and South Africa. 448 patients were randomised to BCT and 420 to MRM. Randomisation was done centrally, stratifying patients by institute, carcinoma stage (I or II), and menopausal status. BCT comprised of lumpectomy and complete axillary clearance, followed by breast radiotherapy and a tumour-bed boost. The primary endpoint was time to distant metastasis. This analysis was done on all eligible patients, as they were randomised. Findings After a median follow-up of 22·1 years (IQR 18·5–23·8), 175 patients (42%) had distant metastases in the MRM group versus 207 (46%) in the BCT group. Furthermore, 506 patients (58%) died (232 55% in the MRM group and 274 61% in the BCT group). No significant difference was observed between BCT and MRM for time to distant metastases (hazard ratio 1·13, 95% CI 0·92–1·38; p=0·23) or for time to death (1·11, 0·94–1·33; 0·23). Cumulative incidence of distant metastases at 20 years was 42·6% (95% CI 37·8–47·5) in the MRM group and 46·9% (42·2–51·6) in the BCT group. 20-year overall survival was estimated to be 44·5% (95% CI 39·3–49·5) in the MRM group and 39·1% (34·4–43·9) in the BCT group. There was no difference between the groups in time to distant metastases or overall survival by age (time to distant metastases: <50 years 1·09 95% CI 0·79–1·51 vs ≥50 years 1·16 0·90–1·50; overall survival <50 years 1·17 0·86–1·59 vs ≥50 years 1·10 0·89–1·37). Interpretation BCT, including radiotherapy, offered as standard care to patients with early breast cancer seems to be justified, since long-term follow-up in this trial showed similar survival to that after mastectomy. Funding European Organisation for Research and Treatment of Cancer (EORTC).
Summary Background Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ...ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial. Methods Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870. Findings Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9–14·7), 376 (163 invasive 122 ipsilateral vs 39 contralateral, 197 DCIS 174 ipsilateral vs 17 contralateral, and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio HR 0·41, 95% CI 0·30–0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19–0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22–0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45–1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58–0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51–0·86; p=0·03) and contralateral tumours (0·44, 0·25–0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66–1·38; p=0·8). No data on adverse events except cause of death were collected for this trial. Interpretation This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision. Funding Cancer Research UK and the Australian National Health and Medical Research Council.
Important differences have begun to emerge concerning the molecular profile of female and male breast cancer which may prove to be of therapeutic value. This review examined all the available data on ...the genomics of MBC. Most male cancers are ER+ve but without a corresponding increase in PR positivity and only a weaker association with estrogen-controlled markers such as PS2, HSP27 and Cathepsin-D. HER2 +ve cancers are rare in males and the role of androgen receptor is controversial. Although the Luminal A phenotype was the most frequent in both MBC and FBC, no Luminal B or HER2 phenotypes were found in males and the basal phenotype was very rare. Using hierarchical clustering in FBC, ERα clustered with PR, whereas in MBC, ERα associated with ERβ and AR. Based on limited data it appears that Oncotype DX is effective in determining recurrence risk in selected MBC. In future, tailored therapies based on genomics will probably yield the most promising approach for both MBC and FBC.
PDF
