Previous epidemiological studies have failed to specify the extent of carcinogenic risk from combined (HRT) or estrogen replacement therapy (ERT) for the lobular and ductal types of breast cancer. This study analyzed data from a population-based case-control study based on case ascertainment through a tumor registry serving 13 counties in western Washington state, part of the Surveillance, Epidemiology, and End Results (SEER) Program sponsored by the National Cancer Institute. A total of 537 women ranging in age from 50 to 64 years who were diagnosed in 1988 to 1990 as having primary breast carcinoma were interviewed along with 492 randomly selected women without breast cancer. The groups were matched by 5-year age groups. HRT generally consisted of conjugated estrogens and, in the combined regimen, medroxyprogesterone acetate.
The only distinguishing patient features were a later age at the first term pregnancy and at menopause for women with lobular breast cancer and a higher body mass index and greater chance of a family history in those with ductal carcinoma. Either estrogen or combined HRT had been used by 73 and 51 percent of these groups, respectively, and by 58 percent of control women. Women who had used combined HRT at any time were at increased risk of lobular breast cancer (odds ratio [OR], 2.1) but not ductal carcinoma. The OR for lobular carcinoma in women using only combined HRT for at least 6 months was 2.5. Women who had used estrogen (ERT) but not combined therapy had a slightly increased risk of lobular breast cancer (OR, 1.4) that was well within the limits of chance. The risk of ductal carcinoma was moderately reduced (OR, 0.6). Risk estimates were basically unchanged when only invasive cancers were analyzed.
The effect of combined HRT on breast cancer risk may be limited to an increase in lobular carcinomas. Armed with this knowledge, clinicians may emphasize the use of ultrasound and magnetic resonance imaging for screening purposes and to follow potential abnormalities.
Cancer 2000;88:2570-2577