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In August 2019, the safety of menopausal hormone therapy (MHT) returned to the scene again. Oncemore, its association with breast cancer risk came up, this time in an article published in the prestigious The Lancet (online in August and printed in September/2019). The subject is not new, and authors of the article are not newcomers either. By representing the Collaborative Group on Hormonal Factors in Breast Cancer, they brought a reanalysis of data from studies on the subject published so far.1 In summary, they evaluated data from 58 studies, out of which 24 were prospective and 34 were retrospective studies, covering almost 144 thousand postmenopausal women with breast cancer (cases) and close to 425 thousandwithout the disease (controls). A higher risk for developing breast cancer was found among MHT users. Women taking combinedMHT for 1 to 4 years had a relative risk (RR) of 1.60with a 95% confidence interval (CI) from 1.52 to 1.69, and for estrogen alone, it was observed a RR of 1.17 (95%CI: 1.10–1.26). For more prolonged use (5 to 14 years), RRs were 2.08 and 1.33, respectively.1 Thefirst important pointwhen evaluating this study is the fact that it is a reanalysis of data from other studies. In other words, data from other 58 studies were obtained and compiled, a total databasewas generated, and then analyzed. This was not a meta-analysis or systematic review, neither were data obtained from a same population at the same time or using the same method. Soon after publication, the International Menopause Society (IMS) came public with their interpretation2 and found an echo in the Associação Brasileira de Climatério (SOBRAC, in the Portuguese acronym), which endorsed the IMS position and translated it into Portuguese under authorization.3 In their comments, the IMS mentioned that much information brought in the recent article is not new.2,3 In fact, the previous publication of the Collaborative Group on Hormonal Factors in Breast Cancer itself, dating from 1997 and covering 51 studies brought similar data, with a RR of 1.35 for breast cancer associated with MHT use for 5 years.4 The Million Women Study also found similar values. The RR for breast cancer inMHTuserswas 1.66, in combinedMHT users it was 2.00, and in users of estrogen MHT alone the RR was 1.30.5 What differs in the study published in The Lancet in 2019 regards the use of estrogen alone, because in this study, the use of estrogen alone presented higher risk, as well as the observational studies previouslymentioned. However, in the Women’s Health Initiative (WHI), the only large randomized study that assessed MHT effects on the risk for breast cancer, this effect was not observed. In the WHI, the RR for invasive breast cancer in users of estrogenMHT alone compared with placebo was 0.80 (95%CI: 0.62–1.04).6 In time, the WHI revealed that estrogen plus progestogen MHT increased the risk, but to a lesser extent than that reported by the Collaborative Group last August.7 Note that data from no randomized study, not even from the WHI, were included in this 2019 reanalysis of the Collaborative Group. On the other hand, although this article did not bring much novelty in terms of MHT-associated breast cancer risk, there is a problem thatmay seemmore relevant from the IMS perspective: most of the MHT assessed does not represent the most common current practices for this type of therapy. This is a result of the fact that in the Collaborative Group reanalysis, the median year of diagnosis of breast cancer cases for the entire database was 2002, whereas for retrospective studies, the median was year 1995. For American prospective studies, the median of the year of breast cancer diagnosis was 1999, and for Europeans it was 2007. Furthermore, in prospective studies, the average time of using MHT was 10 years in users diagnosedwhile using the therapy, and 7 years in former users.1 Therefore, much of the exposure to MHT preceded the first publication of the WHI study, after which the prescription practices changed substantially.2,3 Another relevant criticism of this reanalysis involves the context of womenwho startedMHT before the age of 45. In the presentation of results, the effect of MHT in this context was compared with women in the same age group that were not

Hormone Therapy, Breast Cancer Risk and the Collaborative Group on Hormonal Factors in Breast Cancer Article