Impact of Menopausal Status on Risk of Metastatic Recurrence of Breast Cancer

Chunhuan Lao, MSc, PhD; Mark Elwood, MB, MD, DSc, FRCP (Canada), FAFPHM; Marion Kuper-Hommel, MB, PhD, FRACP; Ian Campbell, MB, FRACS; Ross Lawrenson, MBBS, MD, (London) DRCOG, Dip Comm Health (Otago) FRCGP, FFPH, FAFPHM


Menopause. 2021;28(10):1085-1092. 

In This Article

Abstract and Introduction


Objective: Menopausal status at diagnosis is an important factor for the management of breast cancer in younger women, and may affect the prognosis for these women. We aim to examine the association of menopausal status and risk of metastatic relapse for stage I-III breast cancer.

Methods: We included women diagnosed with stage I-III breast cancer at 45 to 55 years in the Auckland and Waikato Breast Cancer Registers. Cumulative incidence of metastatic relapse was examined by age group and by menopausal status after stratifying by estrogen receptor (ER) and progesterone receptor (PR) status. Cox proportional hazards model was used to estimate the adjusted hazard ratio of metastatic relapse by menopausal status after adjustment for age, ethnicity, year of diagnosis, socioeconomic status, public/private hospital treatment, mode of detection, cancer stage, grade and human epidermal growth factor receptor 2 status.

Results: We have identified 5,309 eligible women: 2,799 premenopausal, 929 perimenopausal, and 1,581 post-menopausal. There was significant difference in risk of metastatic recurrence between menopausal statuses for ER+ and/or PR+ cases, with a 10-year cumulative incidence of 11.2% for premenopausal, 12.4% for perimenopausal, and 15.6% for postmenopausal women. The adjusted hazard ratio of metastatic recurrence for postmenopausal compared to premenopausal women was 1.38 for ER+ and/or PR+ cases. Age did not affect the risk of metastatic relapse for ER+ and/or PR+ cases but affected the risk for ER- and PR- cases with a hazard ratio of 0.94 per year.

Conclusions: Women with earlier age at menopause, and ER+ and/or PR+ stage I-III breast cancer were more likely to develop metastatic breast cancer. Age increased the risk of metastatic relapse for women with ER− and PR− disease, but not for ER+ and/or PR+ cancers.


Breast cancer is the most commonly diagnosed cancer in New Zealand women.[1] Approximately 95% of patients have stage I to III disease at diagnosis.[2] Some of these patients may experience metastatic relapse after treatment for early stage disease. The risk of metastatic recurrence is associated with stage at primary diagnosis, biomarker subtype, age at diagnosis, ethnicity, and other factors.[3–5] For example, regional breast cancer (spread to regional lymph nodes or adjacent tissues, includes locally advanced disease) has more than three times the risk of developing metastatic disease compared to localized cancer (node-negative tumor confined to breast tissue).[3] Human epidermal growth factor receptor 2-positive (HER2+) non-luminal and triple negative breast cancers have a higher risk of metastatic relapse than other subtypes. A German study found that the 10-year cumulative incidence of metastatic relapse was 16.2% for HER2+ non-luminal stage I to III breast cancer and 13.8% for triple negative disease compared to 6.6% for hormone receptor positive luminal type breast cancer.[4] Hormone receptor positive cancers may receive signals from estrogen and/or progesterone that promote their growth, but hormone receptor negative cancers do not receive signals.[6]

The impact of menopausal status at diagnosis on breast cancer prognosis has not been investigated. Menopausal status has, however, been reported to affect the risk of breast cancer and the choice and effects of treatments for breast cancer.[7] Natural menopause usually occurs between the ages of 45 and 55 years. Women who experienced menopause after the age of 55 were found to have an increased risk of breast cancer.[8,9] That is probably because women who have late menopause have been exposed to more estrogen that may promote breast cancer.

Menopausal status at diagnosis is an important factor for the management of breast cancer in younger women, and may affect the prognosis for these women. This study aims to examine the impact of menopausal status on metastatic recurrence for women diagnosed with stage I-III breast cancer at the age of 45 to 55 years.