Better prognosis in ERT/HRT users diagnosed with breast Cancer

Although most observational studies have failed to show a link between ERT/HRT and breast cancer, HRT has been associated with an increased relative risk in some studies. There is some evidence that risk increases at 10 to 15 years of ERT/HRT, but this is neither consistent, nor does it correct for increased lifespan due to ERT/HRT. Regardless of risk, the prognosis of diagnosed cases is better in women taking ERT/HRT.

Other studies show that HRT may even lower the risk of breast cancer. Overall, while investigators may differ in their view, there is no convincing evidence that contemporary doses of ERT/HRT increase the rate of breast cancers in women, and this is without correction for level of risk.

The lower cell-proliferation rate and smaller tumor size found in estrogen receptor (ER)-positive tumors from current HRT users suggest a direct ER-mediated growth inhibitory effect of HRT on established breast tumors. This may at least partly explain why breast cancer in women taking HRT has a more favorable clinical course than it does in nonusers. Although some literature indicates that tumors in HRT users are biologically less aggressive, it is less clear whether HRT alters the tumor features early during carcinogenesis or modulates growth and dissemination in established malignant tumors.

Several other explanations have been presented for the less advanced clinical stage and increased survival time reported in breast cancer patients who take HRT. The association between HRT and tumor size may partly reflect earlier diagnosis due to better medical surveillance and awareness of breast cancer in general. Also, tumors in HRT users were more often detected during screening. Women taking HRT have more frequent mammographic or other examinations for breast cancer. It is a well-established fact that slow-growing tumors are detected at a smaller size. Thus, the relationship of HRT to tumor size may be secondary to the effect on proliferation rate.

When progestin is combined with estrogen

Although estrogen was long the focus of attention regarding increased breast cancer risk, studies have also questioned whether the addition of a progestin - but generally not progesterone - increases breast cancer risk. Although there has been such concern, it is not borne out by the data.

To be sure, this global view of the data does not represent specific positive studies. For example, in the case of ERT or HRT, there are some studies that go against the grain of the majority: A recent reanalysis of data from the landmark Nurses’ Health Study showed that more than 5 years’ use of estrogen plus progestin increased the relative risk of breast cancer by 9% per year, but estrogen alone increased the risk by 3.5%. A second study found that the relative risk of breast cancer rose 24% for every 5 years women took estrogen plus progestin. In contrast, women taking an estrogen-only regimen had a considerably smaller additional risk of 6%. Another similar, more recent study based on data from 46,000 women in the Breast Cancer Detection Demonstration Project also showed that estrogen plus progestin increased breast cancer risk beyond that for estrogen use alone. When the researchers categorized women by weight, however, any difference between estrogen-only and estrogen plus progestin disappeared among heavier women. The increased risk was in lean women (body mass index < 23) or in women who used progestin cyclically, which may increase risk by inducing mitotic changes.

The American College of Obstetricians and Gynecologists does not recommend a change in clinical practice based on recent estrogen-progestin studies. Most often, says ACOG, the benefits of adding a progestin to the HRT regimen will outweigh the risks for women with a uterus. Finally, there is an important generally agreed upon result of observational studies: Women in whom breast cancer develops while taking ERT or HRT will as a group have a better prognosis and less aggressive lesions. At the very least, this indicates that many factors are at play in the ductal epithelium of women on ERT/HRT. Some of these effects may be healthful in the face of endogenous influences on breast cancer development.