More evidence is in showing that progestin included in hormone replacement therapy is linked to breast cancer, according to research published in the journal Cancer.

Postmenopausal women taking the combination estrogen and progestin hormone replacement therapy are at an increased risk for lobular breast cancer, a less aggressive type of cancer than ductal breast cancer, according to researchers.

Researchers at the Fred Hutchinson Cancer Research Center report that a specific formula of hormone replacement therapy called combined estrogen and progestin hormone replacement therapy is linked to an increased risk of lobular breast cancer.

In women who have used the therapy for five years or more, those who used the continuous formula that includes progestin daily for more than 25 days per month were at a greater risk than women who used the sequential formula with fewer than 25 days per month of progestin daily. There was no link to any type of breast cancer for women who use or used estrogen only hormone replacement therapy.

In a large, multicenter study called the Women's Contraceptive and Reproductive Experiences (CARE) Study, researchers studied the relationship between types of postmenopausal hormone therapy and types of breast cancer. Data was collected on 4,575 postmenopausal women ages 35 to 64, diagnosed with their first incidence of breast cancer and 4,682 postmenopausal women with no history of breast cancer.

Researchers conducted interviews with the study participants and information was gathered on menstrual, contraceptive and reproductive histories, medical history, family history, demographic data on smoking status, alcohol use as well as history on the type of hormone replacement therapy used.

Combination hormone replacement therapy use for six months or more was linked with a significantly increased risk for lobular cancer but not ductal cancer. Women who used combination hormone therapy for six months to five years were 1.6 times more likely to develop lobular breast cancer than women who never used hormone replacement therapy. Women who used combination hormone replacement therapy for greater than five years were 2.0 times more likely to develop lobular breast cancer than women who never used hormone replacement therapy.

Continuous use of combination hormone replacement therapy (use of progestin more than 25 days or more per month) was linked with 2.5 times greater risk of lobular breast cancer when used for five or more years. After adjustment for age at menopause, the risk increased to 3.2 times that of women who did not use any hormone replacement therapy. Sequential use of combination hormone replacement therapy (use of progestin fewer than 25 days per month) was linked with 1.5 times greater lobular breast cancer risk than no hormone replacement therapy.

Estrogen replacement therapy was not linked with an increased risk of breast cancer of any type, regardless of the length of use. For women who used estrogen replacement therapy in the past or present, regardless of whether they had ever used combination hormone replacement therapy, there was a slight reduction of cancer risk seen.

"Our study, in agreement with three others, indicates the adverse effect of hormone replacement therapy may be confined to risk or lobular or mixed lobular breast cancer, histologies that are less common, more likely to be estrogen receptor positive, and to have more favorable prognosis than ductal carcinoma," concluded the authors. "Also in agreement with these studies, we did not find an increase in risk of ductal breast cancer associated with use of unopposed estrogen."

Researchers recommend further investigation in older women who have used combination hormone replacement therapy over the long-term since the use of continuous progestin therapy is relatively recent.

Other sources: Cancer