University of Virginia Health System

Lobular Breast Cancer Linked to HRT Use

Not only does hormone replacement therapy raise the risk of breast cancer in postmenopausal women, it raises the risk of a specific type of malignancy called lobular breast cancer.

The study is one of the largest to focus on lobular cancer, which accounts for about 15 percent of all cancers.

Ductal cancer is the most common form of breast cancer, accounting for 70 percent of all cases.

Lobular cancer develops in the areas of the breast that contain milk-producing glands and is more likely to be estrogen-receptor positive and therefore responsive to targeted treatments, resulting in an 11 percent lower death risk compared with ductal cancer.

Ductal cancer develops in the ducts that carry milk from the lobules to the nipple and is more difficult to detect.

Combined Hormones Greatly Increase Risk

"We found that women who were using combined estrogen and progestin hormone therapy had a nearly 300 percent increased risk in their risk of lobular cancer, but only a 40 percent increase in their risk of ductal cancer," says study author Dr. Christopher Li. "There is clear, strong, consistent evidence that using combined estrogen and progestin hormone therapy increases a woman's risk of breast cancer."

It is less well-known how these hormones influence risk of different types of breast cancer.

"This is basically another confirmation of previous information," adds Dr. Jay Brooks of Ochsner Health System. "People who take combined estrogen and progestin are running a significant risk of cancer and heart disease. They really need to know that."

Others, however, downplayed the results.

Dr. Steven Goldstein - author of "The Estrogen Alternative and Could It Be... Perimenopause?" - found nothing new in the study.

"It doesn't change the current recommendations, which are that we should use hormone therapy in the lowest effective dose; for the shortest period of time possible; and consistent with patient treatment goals with reevaluation periodically," he says.

Previous studies, namely the Women's Health Initiative (WHI), found that combined estrogen and progestin hormone replacement therapy increased the risk of breast cancer in postmenopausal women.

Further studies have indicated that the risk is greater with lobular carcinoma than with ductal carcinoma, but these studies have not been definitive.

The rates of both invasive lobular carcinoma (ILC) and invasive ductal-lobular cancer (IDLC) increased 52 percent and 96 percent, respectively, from 1987 to 1999 in the U.S.

Invasive ductal carcinoma (IDC) increased only 3 percent during the same period, according to the study.

Since the WHI results were announced in 2003 and 2004, HRT use has declined 38 percent to 68 percent in the U.S. But 57 million prescriptions for postmenopausal HRT are still filled each year, according to the study.

JoAnn Pinkerton, M.D., Director of The Women's Place Midlife Health Center at the University of Virginia Health System, says the WHI has affected which women receive hormone therapy. 

"Since the WHI, we have become much more selective about who received hormone therapy - [limiting it to] those women with significant bothersome hot flashes, mood disturbances or bone loss," she says. "Our guideline is similar to what the FDA recommends - to use the lowest dose for the shortest period of time to meet treatment goals. Today's women are fortunate that we have half-dose and even quarter-dose products available, which hopefully decreases the risk or allows longer-term use if needed."

Pinkerton says HRT is still recommended for women under 60 or within 10 years of menopause if they meet certain criteria. Criteria include moderate to severe hot flashes/night sweats (more than seven per day or 50 per week) associated with fatigue, sleeplessness, mood disturbances or ongoing bone loss that can't be successfully treated with calcium, Vitamin D and exercise.

Study Findings

Li looked at more than 1,500 postmenopausal women: 1,044 with breast cancer and 469 in a control group for comparison.

Among the women with breast cancer, 324 had lobular cancer, 196 had mixed ductal-lobular cancer, and 524 had ductal cancer. The women were ages 55 to 74 and had been diagnosed between 2000 and 2004.

Women using combined hormone therapy had a 2.7-fold increased risk of lobular cancer and a 3.3-fold increased risk of mixed ductal-lobular cancer.

The increased risk was seen only in women who had used combined HRT for three or more years.

In women who had mixed cancers, HRT increased the risk of tumors that were primarily lobular but not those that were primarily ductal.

Current use of combined HRT was associated with about double the risk of tumors that were mostly lobular (although this was not considered statistically significant), about a fivefold increased risk of mostly ductal tumors and a 7.7-fold increased risk in tumors that were mixed in features.

Like the WHI, this study did not show an increased risk of breast cancer in women who were taking estrogen-only hormone therapy, which is only recommended for women who have had a hysterectomy.

To read a patient story, get additional information on breast cancer treatment or learn about UVA's Breast Care Program, visit www.uvahealth.com. 

UVA also offers a free, confidential risk assesment through the region's only High Risk Care program to determine if you have a higher-than-normal personal risk of developing breast or ovarian cancer. This free service is particularly encouraged for women with a strong family history of breast or ovarian cancer. To arrange the free screening, call 434-982-0808.

Women can learn more about their unique risks for heart disease - and how to better manage those risks - through Live Red, a new UVA heart-health initiative. You'll learn how heart attack symptoms can be different for women than for men, and you can take an online risk assessment to learn your personal heart disease risk factors.

There, you can sign up for Club Red, our free heart-healthy club for women. Benefits include tips from UVA healthcare providers and a gift package to help you live red in style.

Always consult your physician for more information.