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Treatment trends and prognostic findings illuminate male breast cancer journey

By Andrew D. Bowser

Photo Credit: pixelheadphoto digitalskillet)

Men with breast cancer face an exceptionally challenging journey with fewer signposts to guide the way, compared with their female counterparts. Because of the rarity of male breast cancer (1% of all breast cancer cases), prospective clinical trials specific to men have been lacking at a time when there have been significant advances in the understanding and treatment of female breast cancer.

Consequently, there are relatively fewer data available to inform prognosis or treatment of breast cancer therapy in men – though findings just released from one of the largest-ever studies of male breast cancer are providing some new insights that could inform care.

Results of the retrospective analysis, which included 10,873 male patients with breast cancer diagnosed between 2004 and 2014 in the National Cancer Database (NCDB), highlight a number of distinctive prognostic factors in this patient population. The analysis also illustrates an evolution in care over the past decade marked by increased use of total mastectomy, radiotherapy after breast-conserving surgery, endocrine therapy, and genomic testing.

The study also provocatively found that male breast cancer (MBC) patients had benefit from radiotherapy larger than expected based on studies of female breast cancer and, conversely, found that nearly one-third of men with ER estrogen receptor (ER)–positive disease received no endocrine therapy.

“The results of the current study highlight unique practice patterns and factors associated with prognosis in patients with MBC, furthering our understanding of the treatment and prognosis of MBC and identifying unanswered questions for future research,” wrote the investigators, led by Siddhartha Yadav, MD, of Mayo Clinic, Rochester, Minn., in a report appearing in Cancer.

Male breast cancer: Demographics and treatment trends over time

With a median age of diagnosis in the mid-60s, a preponderance of ER-positive disease (89%), and a majority of cases (about 81%) being stage I or II, the demographics of the nearly 11,000 patients in this analysis are similar to those reported in previous studies on male breast cancer, according to investigators.

Mastectomy was performed in about two-thirds of the patients (71.3%), which stands in contrast to female breast cancer, in which about two-thirds would undergo breast-conserving surgery, investigators noted in their report.

Rates of total mastectomy in these male breast cancer patients slowly but significantly crept upward during 2004-2014, with an average annual increase of 0.8%. Contralateral prophylactic mastectomy, seen in 6.1% of patients, increased significantly, with an average annual increase of 10.4%. By contrast, there was no change in the rate of sentinel lymph node surgery and axillary lymph node dissection.

Mastectomy was performed in about two-thirds of the patients (71.3%), which
stands in contrast to female breast cancer, in which about two-thirds would
undergo breast-conserving surgery

Adjuvant radiotherapy was given to nearly 40% of the male breast cancer patients in the study cohort. The percentage undergoing radiotherapy after breast-conserving surgery in 2004 was 66.0%, increasing significantly over time to 74.6% in 2014, investigators wrote; however, there was no change over time in the proportion of patients aged 70 years or older with ER-positive tumors who received radiotherapy after breast-conserving surgery.

Chemotherapy was given to about 45% of the male breast cancer patients in this study, with no change seen over the 2004 to 2014 time period in the proportion receiving chemotherapy, according to investigators. However, use of adjuvant endocrine therapy increased significantly from 48.6% in 2004 to 69.5% in 2014. In addition, there was a significant increase in use of Oncotype DX testing between 2010 and 2014, and for those patients with a recurrence score of 31 or greater, 72.7% received chemotherapy, compared with just 4.7% of patients with scores under 18.

Survival in a male breast cancer cohort

Overall survival did not significantly change over the 2004 to 2014 time period evaluated in this study, with a 5-year overall survival of 79.1% for the entire cohort, and a median overall survival reaching 12.1 years, according to Dr. Yadav and colleagues.

Factors linked to poorer overall survival included older age, black race, high tumor grade, high tumor and lymph node classifications, undergoing mastectomy, and a higher score on the Charlson Comorbidity index, they said.

Conversely, factors associated with better survival included receiving chemotherapy, endocrine therapy, or radiotherapy; progesterone receptor (PR)–positive tumors; and living in a high-income area, investigators reported.

Taking a closer look at disease stage, investigators found in multivariate analysis that chemotherapy was linked to improved overall survival in those with Stage II or III ER-positive tumors who received both surgery and endocrine therapy. Radiotherapy given after breast-conserving surgery was associated with increased overall survival, regardless of disease stage.     

Treatment opportunities and gaps in care?

Adjuvant radiotherapy was associated with a magnitude of overall survival benefit “greater than expected” based on previous studies in female breast cancer, according to investigators (multivariate analysis: hazard ratio, 0.82; 95% confidence interval, 0.74-0.90; P less than .001).

“Even among patients with stage I disease, the survival advantage was pronounced,” Dr. Yadav and coauthors reported.

These findings suggest that, regardless of male breast cancer stage, radiotherapy needs to be considered among patients who undergo breast-conserving surgery, similar to what is recommended for female breast cancer, they wrote.

Only about 70% of the male breast cancer patients in this study undergoing breast-conserving surgery were reported to have received adjuvant therapy, they added.

In a similar vein, the link between use of endocrine therapy and improved overall survival underscores the importance of this treatment in patients with ER-positive male breast cancer, as was demonstrated in previous studies; however, almost one-third of men with ER-positive male breast cancer in this study did not receive such treatment.

“Further studies evaluating factors influencing the decision to use or not use adjuvant endocrine therapy, which to our knowledge is the most effective form of systemic therapy for ER-positive breast cancer, are needed,” the authors suggested in a discussion of those results.

The study by Dr. Yadav and colleagues was partly supported by the National Cancer Institute Specialized Program of Research Excellence (SPORE) in Breast Cancer awarded to the Mayo Clinic. Dr. Yadav reported no conflicts of interest. Coauthors reported disclosures related to Menarini Silicon Biosystems, Genentech, Immunomedics, Pfizer, and Merck.

The median age of diagnosis for men with breast cancer is in the mid-60s.

photo credit: sirtravelalot

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