Educational Information: Risk, Genetic Testing, Genetic Mutation, Prophylactic Treatments

Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

Women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later. The finding, from the Million Women Study (MWS)—a large observational study in the United Kingdom—adds to a growing body of evidence that the use of combined hormone therapy (estrogen plus progestin) to treat menopausal symptoms increases the risk of breast cancer and deaths from the disease. The results appeared in the Journal of the National Cancer Institute on January 28.

The pattern of increased breast cancer risk “was seen across different types of hormonal therapy, among women [in the MWS] who used hormonal therapy for either short or long durations, and also in lean and in overweight and obese women,” Dr. Valerie Beral of Oxford University and her colleagues wrote. Their findings support results from the Women’s Health Initiative (WHI), a randomized clinical trial that, in 2002, first reported evidence linking combined hormone use to breast cancer.

“The new findings underscore the idea that there’s really no safe window of time for women to take combined hormone therapy,” said Dr. Leslie Ford of NCI’s Division of Cancer Prevention and the Institute’s WHI liaison. After the initial WHI results were announced, she noted, some people had argued that hormones may be safer when started at the time of menopause. “The new findings refute that argument,” she added.

WHI and MWS investigators have both reported that breast cancer incidence rates declined rapidly once women stopped taking combined hormone therapy. “It is important for women to know that if they stop using hormones, the risk of breast cancer very quickly returns to where it was before hormone therapy began,” Dr. Ford said.

There has been a discrepancy between the WHI and MWS results to date as to whether estrogen-only therapy raises breast cancer risk in postmenopausal women. WHI reports have found little risk associated with this treatment, whereas the MWS investigators have observed a statistically significant increased risk.

Additional follow-up from the WHI estrogen-only intervention trial should help clarify this issue in the coming years, noted Drs. Rowan T. Chlebowski of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet L. Anderson of the Fred Hutchinson Cancer Research Center in an accompanying editorial.

Study suggests earlier HRT treatment may exacerbate breast cancer risk.

The New York Times (1/29, Grady) reports, "Growing evidence about the risks of breast cancer and other serious illnesses posed by hormone therapy for menopause has led many women to give up the drugs, and many doctors to stop recommending them." Now, new information "from a huge study in Britain suggests that the women thought to be at the lowest risk from hormones may actually be at the highest risk" for breast cancer. The study, published in the Journal of the National Cancer Institute, found that "women with the greatest risk of breast cancer from hormones were those who took them earliest -- before or soon after menopause began."

According to Bloomberg News (1/31, Von Schaper), the study found that "about 55 percent of the 1.1 million women in the study, recruited from 1996 to 2001, reported taking hormone therapy at some time in their lives." Among women in their 50s who "never took hormones, the annual rate of breast cancer was 3 per 1,000." In contrast, women who had started HRT "less than five years after menopause showed a rate of 6.1 per thousand, about double the risk of never-users."

MedPage Today (1/28, Walsh) noted that overall, "15,759 breast cancers were diagnosed, 61 percent in women who had ever used hormone therapy and 45 percent in women currently using the hormones." Notably, breast cancer risk "remained elevated for two years after cessation of therapy" but subsequently fell "to the level seen in women who never used hormones," the researchers reported.

Long-term Follow-up Confirms Breast Cancer Risk Reduction with Raloxifene

Women commonly ask if there is any way to reduce their chances of developing breast cancer if they fall into a higher risk category. Both of the drugs Tamoxifen and Raloxifene have been proven to reduce this risk in some women.  The National Cancer Institute Study of Tamoxifen and Raloxifene trial (STAR) addresses the relative effectiveness of these drugs.  To read the report on this study, please click on the link below.

Patient advocates say BRCA mutation carriers should be fully informed about prophylactic double mastectomy.

NBC Nightly News (10/5, story 7, 3:00, Williams) reported that it is well understood that carriers of abnormal BRCA genes face an "increased risk of breast and ovarian cancer." The "standard course" for such women is "usually watch and wait, with more frequent breast imaging and more biopsies." Now, however, more women are opting for surgery and "while there are no guarantees, a prophylactic double mastectomy...can slash a patient's cancer risk from as high as 80% to practically zero." But, "patient advocates say women need to be fully informed" that the surgery is "not an easy fix." According to Diana Zuckerman, of Cancer Prevention and Treatment Fund, patients "will have to have multiple surgeries for reconstruction, and there is no guarantee that they won't get breast cancer or some other kind of cancer."

For Women with BRCA Mutations, Prophylactic Surgery Reduces Cancer Risk

Prophylactic surgery to remove the breasts and ovaries is an effective way to reduce the risk of breast and ovarian cancer among women with inherited mutations in the BRCA1 or BRCA2 genes, according to one of the largest prospective studies on the subject to date. The findings, published September 1 in JAMA, provide estimates of the benefits of mastectomy and salpingo-oophorectomy (removal of the ovaries and fallopian tubes) in reducing the risk of cancer and death among carriers of disease-associated BRCA1 or BRCA2 gene mutations. These mutations confer a 56 to 84 percent lifetime risk of breast cancer.

The results also show that the risk reduction occurs regardless of whether the mutation is located in the BRCA1 or BRCA2 gene or whether a woman had cancer previously. Researchers at 22 medical centers in Europe and North America tracked nearly 2,500 women with a disease-associated BRCA1 or BRCA2 mutation. Almost half of the women had one of the prophylactic surgeries.

During 3 years of follow-up, none of the women who had a mastectomy developed breast cancer, while 7 percent of the women who didn’t have the surgery were diagnosed with breast cancer. And only 1 percent of the women who underwent risk-reducing salpingo-oophorectomy developed ovarian cancer during 6 years of follow-up, compared with 6 percent of women who did not have the surgery.

“This study reinforces the message that genetic testing has value,” said Dr. Timothy Rebbeck of the University of Pennsylvania, the study’s senior author. Women who know that they have inherited a high-risk mutation can, with the appropriate genetic counseling, take steps to reduce their risk of cancer through prophylactic surgery, he continued.

Although many women choose prophylactic surgery, many do not, the study authors noted. Just 10 percent of the women in the study chose prophylactic mastectomy and 38 percent chose salpingo-oophorectomy. “For women who have these genetic mutations, we think we can save lives,” Dr. Rebbeck stressed. “And that’s an important message.”

The authors of an accompanying editorial in JAMA echoed this message and noted that options for prophylactic surgeries have changed and improved. For example, laparoscopic salpingo-oophorectomy is a relatively low-risk procedure that can be done in an outpatient setting, while new techniques for mastectomy produce a more natural appearance, wrote Drs. Laura Esserman of the University of California, San Francisco, and Virginia Kaklamani of Northwestern University

Recently published study offers "strong evidence" on mastectomy, fallopian tube removal's ability to prolong life.

The Los Angeles Times (10/4, Healy) reports that some women with a high genetic risk of developing breast or ovarian cancer take "dramatic preventive" steps: they have their breasts and/or ovaries, fallopian tubes and often, the uterus removed. Since 2002, the proportion of such women "who have chosen a strategy of preemption to protect themselves from their high genetic risk of cancer has grown from virtually zero to at least one in 10." Although the "approach seems sensible enough," many "women choosing this route have done so amid uncertainty about its ultimate ability to save lives." But "a study published last month in the Journal of the American Medical Assn. finally offered strong evidence that such radical steps do, on average, prolong the lives of women with high-risk versions of the BRCA1 and BRCA2 genes."

Early puberty's link to increased breast cancer risk examined.

In a separate article, the Chicago Tribune (9/22, Elejalde-Ruiz) reports that there is more evidence which suggests the "earlier a girl gets her first period, the greater her risk of developing breast cancer later in life." So, "given reports that more girls are hitting puberty earlier, does that mean that more women might develop breast cancer, and at an earlier age?" The answers, as with many medical questions, are yes, no, and maybe," because it is a "complicated connection to make. A host of other factors contribute to elevated breast cancer risk, including obesity, lifestyle, and genetics, that might also be tied to the age a girl gets her first period. Teasing apart the risk factors will take a long time."

Breast cancer prevention drugs remain "virtually invisible" among Americans.

The Los Angeles Times (10/4, Healy) reports, "For women who worry about becoming the oft-quoted '1 in 8' who will develop breast cancer in her lifetime, two well-established drugs can do for breast cancer what statins and blood pressure drugs do for heart attacks and strokes: drive down their odds of happening." But, while "cardiovascular medications are aggressively advertised, widely prescribed and talked about freely among friends and co-workers," tamoxifen and raloxifene are "virtually invisible on the American pharmaceutical landscape." According to experts, this reality can be attributed to various reasons that involve "optimism, mistrust, and a misunderstanding of how breast cancer risk is calculated." Notably, "in the coming years, researchers expect a new class of drugs -- aromatase inhibitors -- may prove even more effective than raloxifene and tamoxifen at driving down breast cancer risk, cutting it by 70%."

Breast density associated with higher breast cancer risk.

The Washington Post (10/7) "The Checkup" blog reports, "A study published this morning in the journal Cancer Epidemiology, Biomarkers & Prevention shows that among women who have had breast cancer, higher breast density appears to raise the risk of a subsequent breast cancer, especially in the breast that was not affected by the first cancer." For women who have dense breasts, physicians will often order "a breast MRI or ultrasound in addition to [a] regular mammogram to detect abnormalities that the mammogram cannot."

Hormone Therapy Increases Breast Cancer Risk for Women with Dense Breasts

Women who have dense breasts according to a system radiologists use to score mammograms, the Breast Imaging Reporting and Data System (BIRADS), are at an increased risk of developing breast cancer compared with women whose breasts are of average density. And hormone therapy (HT) after menopause, in particular estrogen plus progestin, also increases the risk of breast cancer. Now a report from the NCI-funded Breast Cancer Surveillance Consortium (BCSC) shows that the combination of these two factors increases breast cancer risk by up to twofold. The study appeared online July 19 in the Journal of Clinical Oncology.

The BCSC team, led by Dr. Karla Kerlikowske of the University of California, San Francisco, examined data from seven registries that represent more than 580,000 women and nearly 1,350,000 screening mammograms. The women were age 30 or older, had normal body-mass indices, and completed questionnaires to report menopausal status, surgical histories, and their use of HT.

The association between breast density and cancer risk was strongest for premenopausal women and women using HT after menopause. In the study, premenopausal women with low or average breast density had a 5-year cancer risk ranging from 0.3 to 1.5 percent, compared with a range of 0.9 to 3.1 percent for women with dense or very-dense breasts. The researchers found that postmenopausal women with low or average breast density who used HT had 5-year risks ranging from 0.3 to 2.5 percent, whereas women with dense or very-dense breasts had a risk ranging from 1.1 to 4.4 percent. (Risk was slightly higher for those who used estrogen plus progestin versus estrogen alone.) However, whether they used HT or not, the risk of breast cancer was low for postmenopausal women who had low breast density.

How HT and breast density act together to increase cancer risk—whether the hormones slow the natural changes in the breast that occur with aging, for example, or whether they spur cell growth in cancer-prone cell types—remains unknown, noted the authors. But, in the meantime, “Postmenopausal women with high breast density may want to consider the added risk of breast cancer when deciding on whether to start or stop [HT], especially estrogen plus progestin,” they wrote.

Immediate post-mastectomy reconstruction may improve breast-cancer-specific survival.

Medscape (10/6, Lowry) reported, "Reconstruction of the breast immediately after mastectomy is associated with significantly improved breast-cancer-specific survival," Canadian researchers found after combing through the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry database. Specifically, "immediate breast reconstruction was associated with a 26% reduction in breast-cancer-specific mortality." In fact, "improved breast-cancer-specific survival was observed in all immediate breast reconstruction patients, compared with those who underwent mastectomy alone," a finding that held "true, regardless of the age of the patient."

Low breast cancer awareness among men may result in delayed treatment.

The Chicago Tribune (9/22) reports, "Men's minimal breast development and negligible exposure to female hormones greatly reduces the likelihood that their breast duct cells will undergo cancerous changes, but it does not completely eliminate the possibility that they can get breast cancer." In fact, "in 2010, approximately 1,970 men will be diagnosed with invasive breast cancer." Indeed, "male breast cancer accounts for less than one percent of all breast cancer cases, according to the American Society of Clinical Oncology," but "because breast cancer awareness in men is much lower than in women" a large percentage of "male breast cancer diagnoses aren't made until the cancer is more advanced." Based on information from the University of Michigan, the Mayo Clinic, and other well known organizations, the Chicago Tribune (9/22) also presents a set of myths and facts regarding the disease.