in a large multicenter French cohort study.
The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.
At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.
In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).
Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).
The findings were published online November 16 in JAMA Network Open.
The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.
“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”
The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.
For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.
“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”
Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.
“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”
These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.
“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”
The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.