Medicines deemed essential to prevent breast cancer

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06 October 2021

5 minutes to read

Source:

Pederson, H. Chemoprevention and Lifestyle for Risk Reduction: Women’s Health Clinicians Have a Role. Presented at the North American Menopause Society Annual Meeting; September 22-25, 2021; Washington DC

Disclosures: Pederson reports that he was a consultant for Myriad Genetics.


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Medicines can play a vital role in preventing breast cancer, Holly J. Pederson, MD, director of breast medical services at the Cleveland Clinic, said at the NAMS annual meeting.

“My goals … are to identify women who will benefit the most from risk-reducing drugs, to recognize the importance of co-morbidities and treatment timing, and to develop strategies to improve absorption and adherence”, said Pederson, who is also an associate professor of medicine at the Case Comprehensive Cancer Center in Cleveland.

Only about 4% of the 16% of women eligible for preventive treatment take it, Pederson said, and reasons for low use include patient fears of side effects and lack of time, experience, or physician comfort. with risk assessment and orders.

Holly J. Pederson

“Even in trials where they used computerized decision support tools to encourage adoption, adoption was extremely low – less than 2% in most studies,” she said.

But absorption is often higher in patients with atypical hyperplasia and lobular carcinoma in situ (LCIS), she said. Additionally, studies involving high-risk specialist counseling at breast centers have shown use rates ranging from 11% to 58%.

Treatments available

Tamoxifen can be used for premenopause and postmenopause, while raloxifene can also be used for postmenopause, Pederson said. The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have also recommended exemestane and anastrozole for the postmenopausal setting.

Premenopausal and postmenopausal women in the NSABP P-1 trial who took tamoxifen had a 50% reduction in invasive and non-invasive breast cancer compared to placebo. Specifically, women with atypical hyperplasia saw an 86% risk reduction, and women with LCIS saw a 56% risk reduction.

In the IBIS 1 trial, tamoxifen and anastrozole protected both premenopausal and postmenopausal women for up to 15 years after stopping the drug. Tamoxifen and raloxifene showed essentially equivalent results in postmenopausal women at 5 years in the STAR P-2 trial, although raloxifene resulted in an overall risk reduction of 38% in long-term follow-up.

Exemestane conferred a 65% risk reduction over 3 years compared to placebo in postmenopausal women in the MAP3 trial. Anastrozole resulted in a 53% risk reduction compared to placebo in postmenopausal women over 5 years in the IBIS 2 trial.

Pederson highlighted the results of a 2019 study involving patients with breast neoplasia, atypical hyperplasia, and lobular and ductal carcinoma who experienced a 50% risk reduction after taking 5 mg doses of tamoxifen for 3 years.

Healthy premenopausal women in the NSABP P-1 trial saw “absolutely no increased risk of serious side effects,” Pederson said. “It’s extremely important to reinforce with your patients. “

Tamoxifen offers postmenopausal women an approximately 1% risk of a blood clot, a 1% to 3% risk of uterine cancer, and a slightly increased risk of cataracts. It can also cause vaginal discharge, not vaginal dryness. Raloxifene has an approximately 1% risk of blood clots, but no increased risk of endometrial cancer.

Pederson also said doctors should be able to manage other side effects such as hot flashes, nighttime hot flashes, arthralgia, and vaginal dryness. She also stressed that “recognition and management can improve adherence” to treatment.

Absolute contraindications to tamoxifen and raloxifene include a history of deep vein thrombosis or pulmonary embolism, thrombotic stroke, retinal vein thrombosis, transient ischemic attack, and known predispositions to coagulation. Pregnancy, lactation, and concomitant warfarin or estrogen therapy are also disqualifying.

Contraindications for tamoxifen and raloxifene include age over 60, obesity and smoking, all of which increase the risk of blood clotting, and unreliable contraceptive methods since tamoxifen is teratogenic.

Benefits of genetic testing

Genetic testing has an important role to play in determining who should also receive treatment. For example, women with ATM and CHEK2 are almost exclusively estrogen receptor (ER +) positive and should consider treatment.

Meanwhile, women with BRCA1 are prone to triple negative breast cancer, especially if they are under the age of 50, although women with BRCA1 over the age of 50 who develop breast cancer are more likely to be ER +.

“So in BRCA1 patients over 50, it is not unreasonable to consider prevention with chemo,” Pederson said.

CDH1 predisposes patients to invasive lobular cancer, continued Pederson, and women with PALB2 and BRCA2 should also be considered for preventative treatment. Doctors should be hesitant to prescribe preventative treatment for women with RAD51C and RAD51D, although BARD1 is a possible indicator among ER + families, Pederson said.

In addition, there are over 300 single nucleotide polymorphisms that can confer very small levels of risk individually but significantly affect risk overall, Pederson said.

In addition to genetic testing, doctors can use the Gail and Tyrer-Cuzick risk models to help decide who should take preventative medications.

“I think that’s really how we’re going to initially incorporate this into our practices,” said Pederson, noting that a combination of the Tyrer-Cuzick risk model and the polygenic risk score (PRS) provided a degree of precision. discriminatory much higher than either. component alone in a study published earlier this year.

Additionally, a 2020 Mayo Clinic study asked whether PRS influenced the willingness of genetically negative women to take preventative drugs.

“Some women’s risk estimate has gone down and that of other women has gone up,” she said. “As expected, in those who had a reduced risk estimate based on the addition of PRS, they were less likely to take preventative drugs, and vice versa, in those who had a higher risk with the addition of PRS. , they were more likely to take preventative medication, ”she said. “I think this is an important direction that we are going to take.”

“So who would we target? “

Pederson called patient selection “key” to prevention strategies.

When the estimated 5-year risk is 3% or more, the United States Preventive Services Task Force said, the benefits of preventative drugs likely outweigh the risks. The ASCO threshold is 5% according to Tyrer-Cuzick’s estimate at 10 years in terms of patients most likely to benefit from it.

According to the NCCN, patients with atypical hyperplasia have a 30% risk of developing breast cancer over the next 25 years, while CLIS has a risk of around 2% per year. Therefore, preventive medication should be encouraged in these patients, unless contraindicated.

“Encourage motivated patients to try the drug for 90 days. Tell them you don’t commit to 5 years, but try it for 90 days. Many patients tolerate it much better than they realize, ”said Pederson.

“Send them a written order if they’re on the fence.” Provide them with not only a simple patient document, but also the test documents, and consider starting at this lower dose and then increasing slowly, ”she continued.

Co-morbidities should also be included in breast cancer risks in shared decision-making conversations, Pederson said. Because it uses their own genomic data, a PRS can help women accept and adhere to treatment.

“So who should we target? Pederson asked. “Patients with atypical hyperplasia and CLIS.” Those with a 5-year Gail risk of 3% or more, a Tyrer-Cuzick risk of 5% or more, or patients with genetic mutations predisposing to ER + tumors – BRCA2, BRCA1 over 50 years, CHEK2, ATM, CDHA and PALB2.

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