Estrogen Alone Poses No Increased Breast Cancer Risk

Web Exclusives
Cristi Radford, MS, CGC

SAN ANTONIO—A re-analysis of the Women’s Health Initiative (WHI)—which found an increased risk of breast cancer and heart disease in women taking hormone replacement therapy (HRT)—suggests that estrogen alone, without progesterone, may actually be protective against breast cancer. 

“This information was downplayed by the WHI at the time. We analyzed the two trials and did tests for interactions, comparing estrogen alone with estrogen plus progestin. We found a significant reduction in risk of breast cancer with estrogen alone, compared with a significant increase with the hormonal combination,” said Joseph Ragaz, MD, of the University of British Columbia’s School of Population and Public Health, Vancouver, Canada, who reported findings at the 33rd annual San Antonio Breast Cancer Symposium.                     

The combined studies involved more than 25,000 healthy women. The first WHI trial (WHI1) evaluated estrogen (Premarin 0.625 mg/day) plus progestin (Provera 2.5 mg/day) versus placebo, and the second (WH2), which was limited to women without a uterus, evaluated estrogen alone (Premarin 0.625 mg/day) versus placebo. A comparative analysis assessed breast cancer rates between the two studies and according to the women’s risk for breast cancer (Gail score), hormone use before the study, and other factors.

 

”The study found that HRT based on estrogen alone was significantly protective against the development of breast cancer, reducing the incidence by 20%; combined HRT, on the other hand, actually increased the risk by 25%,” he said. 

By Gail score, women at low-to-medium risk (<1.75 score) had a relative risk reduction of 29% with estrogen alone, while on estrogen plus progestin their risk increased by 25%, Ragaz reported.

In women without any previous hormone use, estrogen alone was significantly more protective, with a 34% reduction in events. Estrogen plus progestin was associated with a 16% increased risk, he added. 

A subset of patients had a low risk for developing breast cancer, based on Gail score <1.75, no previous HRT before the study, no positive family history of breast cancer, and no personal history of benign breast disease. In these women, the risk of developing breast cancer was reduced by 20% altogether, and by as much as 43% if they had no history of benign breast disease. 

In addition, estrogen alone, at least in some age groups, was significantly protective against coronary heart disease, colorectal cancer, and hip fracture, Ragaz added. 

“A prospective evaluation of HRT is now required to establish the best regimens and formulation of HRT based on estrogen alone, and with or without a safer new progestin combination,” Ragaz said. “It is very important to look into new generation progestins that are more natural.” New compounds—one is called prometrium—are in development, he said.

Based on these findings, he believes that for a subset of women aged 60 and younger estrogen alone might be safely used. In particular, these would be younger women who had undergone hysterectomy and did not need the protective effect of progestin against endometrial cancer

Related Items
“Newer” Ovarian Cancer Genes and Option of Risk-Reducing Salpingo-Oophorectomy
Cristi Radford, MS, CGC
Online First published on May 12, 2016 in Genetic Counseling, Online First
T-DM1 in Metastatic Breast Cancer
Cristi Radford, MS, CGC
TOP - August 2012, Vol 5, No 5 published on August 22, 2012 in Breast Cancer
Exploring the Drug Shortage Crisis
Cristi Radford, MS, CGC
TOP - August 2012, Vol 5, No 5 published on August 22, 2012 in Drug Updates
Pharmacists Can Enhance Compliance With Oral Medications
Cristi Radford, MS, CGC
TOP - June 2012, Vol 5, No 4 published on July 2, 2012 in Best Practices
Abstracts of Interest From the 2012 American Society of Clinical Oncology Annual Meeting
Cristi Radford, MS, CGC
TOP - June 2012, Vol 5, No 4 published on July 2, 2012 in Conference Correspondent
Payer Trends in Oncology: Challenges and Solutions
Cristi Radford, MS, CGC
TOP - Special Issue May 2012, Vol 5, No 3 published on May 24, 2012 in Conference Correspondent
What Pharmacists Need to Know About 7 New Agents
Cristi Radford, MS, CGC
TOP - Special Issue May 2012, Vol 5, No 3 published on May 24, 2012 in Drug Updates
Many Febrile Neutropenia Patients Can Be Treated at Home
Cristi Radford, MS, CGC
TOP - April 2012, Vol 5, No 2 published on April 30, 2012 in Supportive Care
What’s New in Antiemetic Control?
Cristi Radford, MS, CGC
TOP - April 2012, Vol 5, No 2 published on April 27, 2012 in Supportive Care
Eribulin Associated With Less Neuropathy Than Ixabepilone in a Prospective, Randomized Study
Cristi Radford, MS, CGC
TOP - February 2012, Vol 5, No 1 published on February 28, 2012 in Breast Cancer
Last modified: February 20, 2019