Persistent Hot Flashes Increase Breast Cancer Risk in Women

Pam Harrison

January 08, 2019

Postmenopausal women who experience persistent hot flashes are more likely to be diagnosed with breast cancer than women who never experience vasomotor symptoms (VMS), but they are not more likely to die from it, a new long-term analysis from the Women's Health Initiative (WHI) suggests.

At a median follow-up of 17.9 years, women who reported having persistent VMS for a median duration of at least 10 years were 13% more likely to be diagnosed with breast cancer than women who never reported having VMS, even after adjustment for known breast cancer risk factors, such as body mass index (BMI), alcohol use, age, smoking status, and family history of breast cancer, note Rowan Chlebowski, MD, PhD, City of Hope National Medical Center, Duarte, California, and colleagues in their report published online December 28, 2018, in Menopause.

This increase, although slight, was significant, the authors observe.

"I think that this is just another signal that women with persistent hot flashes should be vigilant about breast cancer screening, which we know will lead to early detection and a reduction in breast cancer mortality," Chlebowski told Medscape Medical News.

Analyzing Women in WHI Who Did Not Take HRT

At the present time, studies examining the association between VMS frequency and persistence with breast cancer incidence have been limited "and provide conflicting results," say the authors.

The current analysis involved a total of 25,499 postmenopausal women between 50 and 79 years of age who participated in the Women's Health Initiative (WHI) clinical trials and observational study. A negative mammography was required for clinical trial entry.

None of these women had received hormone replacement therapy (HRT) — those who had taken HRT in the WHI were excluded from this particular analysis.

Women answered a questionnaire at study enrollment about their experience with hot flashes or night sweats, or both, and their age at the time they experienced their first and last hot flash episode.

"Women were categorized as 'persistent VMS' if they reported having moderate or severe hot flashes and/or night sweats within the last 4 weeks before WHI entry and also reported having ever experienced VMS," the investigators observe.

At the time of enrollment, 38% of the women had persistent VMS, a significantly higher proportion than typically reported in the literature, Chlebowski observed.

Over a median of 17.9 years of follow-up, 5.5% of the cohort developed invasive breast cancer, with a higher risk for those with persistent VMS.

The incidence of breast cancer also increased as BMI increased.

And the risk of breast cancer was 26% higher among women who reported current alcohol use versus those who did not, at a hazard ratio (HR) of 1.26, and was 24% higher among nulliparous women, at an HR of 1.24, compared with women who had ever been pregnant.

There were also differences in the types of breast cancer recorded.

Compared with women who reported never having VMS but who went on to develop breast cancer, women with persistent VMS were significantly more likely to have breast cancers with a poor prognosis, for example, estrogen receptor-negative tumors (P = .018), and to present with regional or distant involvement (P = .002), the study authors point out.

And at a median follow-up of 9 years from breast cancer diagnosis, "the risk of breast cancer-specific mortality was higher in women with persistent VMS compared with women who never experienced VMS at an HR of 1.33...but the difference was not statistically significant," the researchers add.

Breast Cancer Risk Factors Similar to CVD Indicators

As a medical oncologist, Chlebowski noted that one of his main goals in performing this analysis was to point out that postmenopausal women who go on to develop breast cancer have many of the same risk factors as women who go on to develop cardiovascular disease (CVD).

Key among these risk factors is obesity.

"Currently, some 40% of postmenopausal women in the United States are obese, which is really kind of incredible compared to even just 20 years ago," Chlebowski said.

"So we have this huge population of postmenopausal women who put themselves at increased risk for breast cancer, which I'm concerned about of course, as well as other 'western' diseases like CVD," he added.

However, unlike the CVD arena with its consistent message of prevention through lifestyle measures, the same message has failed to materialize in the cancer domain, says Chlebowski, even though, in his view, both diseases share a similar constellation of risk factors.

Indeed, "the association of VMS with risk factors common to both cardiovascular disease and breast cancer provides a plausible explanation for an association of persistent VMS with higher breast cancer [risk] seen in the current report," he and his colleagues maintain.

However, given the mixed findings regarding VMS and breast cancer risk in the literature to date, further study of this association is clearly needed, they conclude.

Chlebowski has reported receiving honoraria from Novartis and AstraZeneca and consulting fees from Novartis, AstraZeneca, Pfizer, and Genentech.

Menopause. Published online December 28, 2018. Abstract

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