Men with HR+ breast cancer have high breast cancer─specific mortality risk at 20 years

Breast cancer–specific mortality (BCSM) risk remains high over 20 years in men with stage I─III hormone receptor (HR)–positive breast cancer and the kinetics are different from those seen in women, a population-based study has shown.

“[Due to its rarity], men with breast cancer have been under-represented in clinical trials, whether through explicit exclusion or lack of enrolment in trials that technically allowed men,” said the researchers. “To date, published studies on BCSM beyond 5 years in men with nonmetastatic HR-positive breast cancer have been limited.”

To investigate the risk of late mortality in male breast cancer patients, the researchers conducted a 20-year observational cohort study using population-based data from the Surveillance, Epidemiology, and End Results (SEER) programme. They included 2,836 men diagnosed with stage I─III HR-positive breast cancer (median age at diagnosis, 67 years) from 1990 to 2008. The primary outcome was BCSM. [JAMA Oncol 2024;doi: 10.1001/jamaoncol.2023.7194]

After a median follow-up of 15.41 years, 986 patients (34.8 percent) were alive, 634 (22.4 percent) had died of breast cancer, and 1,216 (42.9 percent) had died of causes not related to breast cancer. The cumulative risk of BCSM by 20 years was 12.4 percent for stage I, 26.2 percent for stage II, and 46.0 percent for stage III breast cancer.

“Much like in women, the risk varies by tumour size, grade, and nodal status,” noted the researchers. “However, the kinetics appear to be different from those in women with higher-stage disease.”

A prior study in women with stage III HR-positive breast cancer showed that the hazard rate of BCSM peaked at 6 percent at approximately 5 years after diagnosis, then decreased over the next 20 years. However, men with stage III breast cancer experienced a peak hazard rate of 6.3 percent at year 4, followed by another peak of 7.5 percent at year 11.

Of note, the bimodal trend was most apparent in men with N3 disease, in whom BCSM risk initially peaked at year 4 with a hazard rate of 9.9 percent. The risk then decreased before elevating to a higher peak of 12.7 percent at year 11. “The late peak occurred across all nodal categories in men with breast cancer, which was observed earlier for each additional nodal category and had a larger hazard magnitude,” added the researchers.

“Reasons for the occurrence of this late peak in HR-positive male breast cancer are unclear,” noted the researchers. Compared with women, men with breast cancer have limited evidence-based endocrine therapy options, with tamoxifen being the preferred agent. Lack of treatment adherence may play a role in the late BCSM risk in male patients with breast cancer. Other possible explanations may include between-gender differences in tumour biological factors.

Treatment guidelines for men with breast cancer have largely been derived from clinical trials in female patients. “Our findings suggest that male patients with stage I─III HR-positive breast cancer face a long-term risk of recurrence and death, which should not be extrapolated from women when counselling patients. Further investigation into better adjuvant treatment options for male patients is warranted,” noted the researchers.