Predictors of permanent menopause after chemotherapy for early-stage breast cancer in premenopausal women

575 Background: Optimal choice of endocrine therapy for early-stage breast cancer differs with menopausal status. While amenorrhea is common during adjuvant chemotherapy, there is currently no available test to establish when menopause is permanent. The aim of this study was to determine the age cutoff after which resumption of menses is unlikely following chemotherapy and to assess what additional risk factors may predict for persistent menopause at 5 years after initiation of chemotherapy. Methods: One hundred patients treated with chemotherapy for early-stage premenopausal breast cancer and who remained alive and free of recurrence at least 5 years from the start of treatment were enrolled. Participants were evaluated for current menstrual status and for baseline potential risk factors for menopause: age at start of chemotherapy, race, BMI, smoking history, age at menarche, irregular menses prior to chemotherapy, presence of menses during chemotherapy, type of chemotherapy regimen, hormonal therapy, ovarian protection during chemotherapy, and number of doses of alkylating agent (cyclophosphamide). Recursive partitioning analysis (RPA) was used to identify the age cutoff that best predicts permanent menopause; additional risk factors were assessed using logistic regression analysis. Results: Median age at start of chemotherapy was 43 (range 26–49). RPA identified age >42 at the start of chemotherapy as a significant predictor of permanent menopause (p < 0.001). Cessation of menses during chemotherapy was also associated with permanent menopause (p < 0.001). Both variables remained significant in multivariate analysis (p < 0.001), with the combination of these factors being associated with a 95.4% chance of permanent menopause. Conclusions: In this series, fewer than 5% of premenopausal patients who were at least 42 years old and who experienced cessation of menses during chemotherapy experienced any return of menses over at least 5 years. Upfront use of aromatase inhibitors as adjuvant endocrine therapy for premenopausal hormone-receptor positive breast cancer warrants further investigation for those who are at least 42 years of age and who experience amenorrhea with chemotherapy. No significant financial relationships to disclose.

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Risk Factors for the Incidence of Breast Cancer: Do They Affect Survival From the Disease?

Journal of Clinical Oncology ◽

10.1200/jco.2006.10.3168 ◽

2008 ◽

Vol 26 (20) ◽

pp. 3310-3316 ◽

Cited By ~ 126

Author(s):

Gillian C. Barnett ◽

Mitul Shah ◽

Karen Redman ◽

Douglas F. Easton ◽

Bruce A.J. Ponder ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Alcohol Intake ◽

Menopausal Status ◽

Oral Contraceptive Pill ◽

Smoking History ◽

Age At Menarche ◽

Published Data ◽

Risk Of Death ◽

Prior Use

Purpose Risk factors that influence the incidence of breast cancer may also affect survival after diagnosis. Methods Data from 4,560 women with invasive breast cancer who had taken part in the population-based Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) breast cancer study were used to investigate the influence on survival of variables related to pregnancy, menarche and menopause, prior use of exogenous hormones, height, weight, body mass index (BMI), smoking history, and alcohol intake. Results In univariate analyses, there was no association between prognosis and age at menarche and menopause, menopausal status at diagnosis, smoking history, or prior use of the oral contraceptive pill. Women whose most recent pregnancy was more than 30 years ago had a 35% reduced risk of dying (95% CI, 8% to 54%) compared with women who had a full-term pregnancy in the past 15 years, and the use of hormone replacement therapy for more than 4 years was associated with a similar risk reduction. BMI was associated with a 3% (95% CI, 1% to 4%) increase in mortality per unit increase. Improved prognosis was seen with increasing current alcohol consumption, with a 2% (95% CI, 1% to 3%) reduction in the risk of death per unit of alcohol consumed per week. Conclusion The apparent benefit of alcohol intake has not been described before, and our data need to be interpreted with some caution. However, our finding that an increase in BMI is associated with a poorer prognosis supports previously published data and suggests that advice on weight loss should be given to all obese patients with breast cancer.

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