Combination hormone-replacement therapy (HRT) made headlines last summer when a landmark Women's Health Initiative study showed that use of the drug boosts a woman's risk of developing breast cancer.
Now, a new study led by Dr. Janet Daling and colleagues in the Public Health Sciences Division reveals that the increased risk is limited to a less aggressive form of the disease known as lobular breast cancer.
The findings help to explain why incidence of this rarer form of breast cancer has increased steadily over the past decade among postmenopausal women in the United States. In contrast, incidence rates for ductal carcinoma, the more common type, have remained steady.
The researchers found that in women under 65, those who used combination hormone therapy for at least six months had about a twofold increased risk of developing lobular breast cancer compared to women who did not use such therapy.
The study appears in the Dec. 15 edition of Cancer. Drs. Kathleen Malone, David Doody and Lynda Voigt, also of PHS, were co-authors.
Although earlier studies, including ones conducted at Fred Hutchinson, indicated a link between combined HRT use and lobular cancer, Daling said that the scope of the current study substantiates its findings.
"This is a much larger study and was conducted more recently than the prior studies, so the risks could be estimated with more precision for each regimen of HRT," she said.
"In addition, we included more people with longer-term use. Also, one third of the women in the study were African-American."
Still, she and her collaborators caution that theirs was a case-control study, which relied on a woman's recall of the types of HRT she had used in the past.
Researchers generally regard randomized trials, in which study participants are randomly assigned - or not - to a particular course of treatment or intervention, as more definitive analyses.
The large, multicenter study, known as the Women's Contraceptive and Reproductive Experiences Study, assessed the relationship between types of postmenopausal hormone therapy and types of breast cancer.
The analysis focused on 2,500 postmenopausal women aged 35-64 years diagnosed with the first incidence of breast cancer and on a similar number of postmenopausal women with no history of breast cancer.
In-person interviews were conducted, and information was collected on menstrual, contraceptive and reproductive histories; medical and family history; alcohol and tobacco use, and detailed history of the type of hormone therapy used, including start and end dates, total duration, dose and pattern of use.
Use of combined estrogen and progestin HRT for six or more months was associated with significantly increased risk for lobular cancer but not ductal cancer.
Compared to women who never used HRT, women who used combination therapy for six or more months were 1.6 times more likely to be afflicted with lobular carcinoma.
In addition, combination HRT that contained daily progestin dosing for 25 or more days per month was associated with a 2.5-fold greater risk of lobular breast cancer when used for five or more years.
Combination therapy that included daily progestin dosing fewer than 25 days per month was associated with 1.5 times greater lobular cancer risk than no use of HRT.
There was no increased breast-cancer risk found among women who took HRT containing estrogen alone.
Although lobular breast cancer is generally less aggressive than ductal breast cancer, Daling said the jury is still out on whether combination HRT use is linked to increased mortality due to breast cancer.
"This histologic type of cancer does have a 15 to 25 percent lower risk of mortality," she said. "However, this may not result in lower mortality overall since the incidence of lobular cancer appears to be increasing due to use of this drug."