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BARCELONA, Spain — More women at high risk for breast cancer should be given preventative endocrine treatment if appropriate, some experts argued at the 15th European Breast Cancer Conference.

“The real question is not whether prevention works. The question is why are we not using it?” said Andrea De Censi, MD, director of the Breast Unit at Champalimaud Clinical Centre in Lisbon, Portugal, during a debate. He maintained that fewer than 10% of women who could be taking preventative endocrine treatment were doing so.

De Censi argued that not using an option that has demonstrated it provides at least a 50% reduction in the development of estrogen receptor-positive breast cancer with a “very nice carryover effect 5 years after treatment cessation” was “not a scientific gap” but “a clinical failure. It is bad medicine.”

At the very least, women need to know about endocrine prevention, said Rebekah Law, MBBS, a clinical research fellow at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, both in London, England.

“The vast majority of women at high risk of breast cancer are simply unaware that this option exists,” Law said. “We have a duty to inform all women that this is a possibility because without doing that we are ignoring one of the very cornerstones of medical ethics,” she added.

Law told Medscape News Europe, “We should be telling all women about endocrine prevention so that they can be empowered to make a choice.”

However Sara Brucker, MD, of Tübingen University Hospital in Tübingen, Germany, said there are clear arguments against the widespread use of endocrine treatment for all women with high-risk breast cancer.

“Our current risk assessment is inadequate. The number to treat is too high and the harms are significant, leading to a poor real-world adherence, and of course, there is no demonstrated survival benefit,” she said.

Rather than chemoprevention, “we should embrace personalized medicine instead: definitive surgery, for example, for those who have the highest risk, and intelligent, risk-based screening for everyone else,” Brucker suggested.

Pascal Pujol, MD, University of Montpellier, Montpellier, France, agreed to a certain degree that endocrine prevention should not be considered for all high-risk women. Pujol was the principal investigator for the LIBER phase 3 trial, which looked at preventative endocrine treatment with the aromatase inhibitor letrozole in postmenopausal women with BRCA1/2 mutations. He was also an investigator for the phase 3 MAP.3 trial of preventative treatment with another aromatase inhibitor, exemestane, in postmenopausal women.

In LIBER, “there was no significant signal” of a benefit for the overall population of the 84 women who had been randomly allocated to endocrine prevention over the 86 women who had been randomly allocated to placebo. The 5-year incidence of invasive breast cancer in the study was a respective 7.8% and 13.1% (P = .416).

“It could not be ruled out that there could be an effect actually in subgroups, but the data were not powerful enough to address this question,” Pujol said, noting that the trial did not reach its planned accrual target and as a result was underpowered.

Pujol proposed that BRCA1/2 carriers were not suitable for endocrine prevention. BRCA1/2 cancers may be hormone receptor-positive, he said, but they appear to be less or not sensitive to the effects of estrogen.

Even in young premenopausal women who had strong family history of breast cancer, the use of preventative endocrine treatment was questionable due to the balance of benefit over risks, Pujol said. Risks included increased morbidity due to estrogen suppression, such as osteoporosis, or an increased risk for endometrial cancer with tamoxifen.

This is not about using the therapeutic dose of the endocrine treatment, said De Censi, who was an investigator for the TAM-01 study, from which 10-year follow-up data were recently reported.

In that study, tamoxifen was given at a dose of 5 mg/d for 3 years, much lower than the 20 mg/d that is generally used therapeutically. Results showed invasive breast cancer among women with ductal carcinoma treated with “baby-TAM” was halved vs placebo.

Prevention potentially helps women avoid surgery, radiotherapy, possible chemotherapy, and all the long-term consequences and psychological distress that accompanies diagnosis and treatment, De Censi and Law argued.

Law said US, European, and UK guidelines list preventative endocrine therapy as an option to be discussed with women. “We have a wealth of evidence,” noting survival should not be the only outcome by which the success of endocrine prevention is measured.

Breast cancer diagnoses come with huge psychological, financial, and health service burdens, she said, adding, “If we can instead give a medication that is, as we say in the UK, ‘cheap as chips,’ why would we not do that? It seems mind-blowing that so few people are taking this.”

De Censi added, “We accept prevention in cardiology, why not in oncology?”

De Censi, Law, and Brucker reported no financial relationships. Pujol reported acting as the principal investigator for the Novartis-sponsored LIBER phase 3 trial and the Pfizer-funded phase 3 MAP.3 trial of preventative endocrine therapy. Pujol also reported acting as an advisor to AbbVie, AstraZeneca, Exact Sciences, Guardant, MSD, Natera, Novartis, and Pfizer and giving talks on behalf of Agendia, AstraZeneca, Bayer, Genomic Health, Myriad Genetics, Guardant, Novartis, OncoDNA, Roche, SeqOne, Takeda, and MSD.

Sara Freeman is a medical journalist based in London.