Postmenopausal breast cancer: a best endocrine strategy?

Postmenopausal, oestrogen receptor (ER)-positive breast cancers account for the majority of the 1·7 million breast cancers diagnosed annually worldwide. Adjuvant endocrine therapy dramatically improves survival among such patients, making it vital to understand the best treatment strategies.

For decades, the Early Breast Cancer Trialists’ Collaborative Group meta-analyses have informed clinical practice in early-stage breast cancer, and the present report1 in The Lancet on over 30?000 women treated with adjuvant tamoxifen, aromatase inhibitors, or a sequence of those agents continues that tradition.

The meta-analysis confirms that, in comparison with tamoxifen alone, aromatase inhibitor-based therapy in the first 5 years reduces the risk of recurrence (rate ratio 0·64, 95% CI 0·52–0·78, during years 0–1; 0·80, 0·68–0·93, during years 2–4) and improves overall survival at 10 years (0·89, 0·81–0·97).

Sequential therapy with tamoxifen and then an aromatase inhibitor during the first 5 years yielded recurrence rates that were nearly the same as those achieved with upfront aromatase inhibitor therapy, with average recurrence rates differing by less than 1% through 7 years of follow-up and without a survival difference.

Because of the enormous size of the individual trials that comprised the meta-analysis—most of the primary studies enrolled between 5000 and 10?000 women—recurrence reductions were already well established,and clinical guidelines recommend that postmenopausal women consider aromatase inhibitor-based therapy within the first 5 years of their adjuvant treatment course, either up front or sequentially after tamoxifen.

Those caring for women with breast cancer realise that the accompanying meta-analysis is missing a key set of data: the patient experience.

Women on anti-oestrogen treatments endure substantial side-effects, including menopausal symptoms such as hot flashes and night sweats.

Aromatase inhibitors, in particular, are also associated with bone pain and arthralgias, vaginal dryness, sexual dysfunction, osteoporosis, bone fracture, and hair thinning. Some of these symptoms can be addressed with specific interventions; others prove resistant and markedly affect quality of life. Treatment-related symptoms are a primary determinant of patient compliance with adjuvant endocrine therapy.
Anecdotal experience suggests that some patients tolerate aromatase inhibitors better than tamoxifen, and vice versa, and that patients intolerant of one aromatase inhibitor might tolerate another, especially after a short treatment hiatus to reset their symptom profile.

Ultimately, the best choice for adjuvant endocrine therapy is a treatment the patient is willing to take.
For most patients, especially as we envision an era of longer durations of endocrine therapy, it will be more important to assure that they are on a tolerable medication than to be unyielding over prescribing a specific bottle that sits untouched in the medicine cabinet.

G Mohan.