Breast Cancer After Menopause

breast cancer
Overweight women are more at risk for developing breast cancer after menopause, according to a new analysis. The risk of cancer rises the greater the weight. Researchers discovered that the most obese women are 86 percent more likely to be diagnosed with breast cancer that is also more advanced.

There has been other research that has linked excessive weight to the risk of breast cancer. Due to a wide range in weight variations, it is critical to be able to confirm that link, because that would imply that women can lessen their risk of breast cancer, according to Marian Neuhauser, from the Cancer Prevention Program at the Fred Hutchinson Cancer Research Center in Seattle. Neuhauser led this particular study.

The newer study was published in JAMA Oncology. The data that had been analyzed by the researchers from the larger, long-term Women’s Health Initiative Study involved 67,142 post-menopausal women between the ages of 50 and 79 years old across the U.S. The researchers ran their study for 13 years. By 2010, breast cancer was diagnosed in 3,388 of the women.

The researcher teams divided the women in the study by body mass index (BMI). A BMI lower than 25 is considered normal. A BMI between 25 and 30 is overweight and anything over 30 is severely obese. Approximately 5 percent of the women in each group were diagnosed with invasive breast cancer during the 13-year study period. However, the risk of being diagnosed with breast cancer was increased with weight.

Women who had a BMI of 35 and higher were 56 percent more likely to be diagnosed with invasive breast cancer during the study, compared to women with a normal body weight. Researchers looked at breast cancer subtypes and found the obese women were 86 percent more likely than normal-weight women to find breast tumors that are driven by progesterone and estrogen.

Progesterone receptor-positive and estrogen receptor-positive breast cancer are the most common forms found in these women. There is not a link between weight and hormone receptor-negative breast cancers.

breast cancer

The use of hormone replacement therapy after menopause, according to researchers, did not change the correlation between weight and breast cancer. However, women of a normal weight who gained 5 percent of their original weight during the 13-year study increased their risk of getting breast cancer to 35 percent.

The reverse, however, did not work in the same way. Women who were overweight and were able to lower their BMI did not reduce their risk of getting breast cancer. Neuhauser reminds readers that the research included in this study was not about weight loss. An entirely different research study that focuses on whether weight loss can reduce the risk of breast cancer needs to be conducted.

Dr. Clifford Hudis told Reuters Health that more studies have to be conducted. The current results are to caution women that once they are overweight, the damage may already have been done. Hudis co-wrote an editorial that went along with this current research study and it said that more research needs to be conducted in order to determine why the increase in body weight increases the risk of breast cancer. Once this correlation is studied and found, solutions can be determined.

A phase II trial showed neoadjuvant TDM-1 effectively treats HER2-positive, hormone receptor (HR)-positive breast cancer. This is effective with or without endocrine therapy, compared to trastuzumab and endocrine therapy. The results of the study were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from May 29-June 2.

An umbrella trial of 5,000 patients using WSG-ADAPT was a sub-study that included patients with HER2-positive and HR-positive early stages of breast cancer. Out of the 376 patients that were enrolled at 48 sites this interim analysis included 130 of these patients. The trial closed early as efficacy had been accomplished. Patients randomly received TDM-1 monotherapy (37 patients), TDM-1 with endocrine therapy (48 patient), or trastuzumab with endocrine therapy (45 patients).

Study presenter, Nadia Harbeck, MD, Ph.D., of the University of Munich, stated that the patients in the study were not a low-risk population. Over half of the patients in the study were post-menopausal and half of those patients had tumors larger than 2 cm.

The rate of pathologic complete response (PCR), defined as a non-invasive tumor in the breast and nodes, was 40.5 percent with TDM-1 alone, 45.8 percent with TDM-1 and endocrine therapy, and 6.7 percent with trastuzumab and endocrine therapy. Harbeck said these PCR rates compared well to other trials in this particular subpopulation.

The results with TDM-1 changed with menopausal status. A significantly higher number of postmenopausal women benefited from using the TDM-1 monotherapy compared to premenopausal women. However, when the endocrine therapy was added, there was no difference to be observed.

There was a low-level of toxicity and seven, grade-three adverse reactions related to the study medications used. All patients completely recovered. Harbeck said that it is not unreasonable to state that their trial proves that therapy de-escalation is a possibility. She says this is the direction that should be pursued for the greatest benefit of the patients.

An MD from the Memorial Sloan Kettering Cancer Center, Shanu Modi, was the discussant for this particular session and she believed the results of this study to be “striking.” She said that it is of interest that only small improvements occurred when the endocrine therapy was added to TDM-1. Harbeck again stressed that the results were only an interim analysis, but the full data set will show a clearer picture of what is actually happening.

breast cancer

Adding the medications palbociclib and fulvestrant doubled survival without the progression of cancer in patients who have been pretreated with HR-positive, and HER2-negative breast cancer in the PALOMA-3 trial the CDK 4/6 inhibitor delayed the progression of the disease by more than five months.

According to the results of the study as they were presented at the 2015 ASCO Annual Meeting and at the same time the results were published in The New England Journal of Medicine, combining palbociclib and fulvestrant is effective for women whose cancer had further progressed before endocrine therapy, according to Nicholas C. Turner, MD, PhD, consultant medical oncologist at the Royal Marsden and Institute of Cancer Research in London.

A double-blind multicenter PALOMA-3 study randomized 521 patients that had metastatic breast cancer, whose cancer had spread while on or after receiving endocrine therapy. In a 2:1 ratio the fulvestrant in addition to palbociclib or a placebo, fulvestrant was given at 500 mg on days 1 and 15 of the first cycle, and then, on day 1 of each cycle after. Patients received oral palbociclib at 125 mg a day for three weeks of each cycle then patients had a week off the medication. Treatment cycles were 28 days for both arms. Goserelin was also given to patients who were pre and perimenopausal.

The baseline information that had been collected between both arms was similar. The median age of the patients was 57 and 56 in the palbociclib and placebo arms. Patients were divided by menopausal status, visceral metastases, and sensitivity to prior hormonal therapy. In both treatment arms, 79 percent were postmenopausal. One prior line of chemotherapy for advanced stages of breast cancer was allowed, 33 percent of the patients had received chemotherapy.

PFS, being the primary outcome, and the secondary objectives focused on overall survival (OS), safety, and response. After 195 PFS events, the trial was concluded as it had been determined the study had met its primary goal.

The PFS benefit was seen no matter what the status of menopause and observations were consistent over all prespecified subgroups. The combination of the palociclib and fulvestrant was well tolerated, according to Turner. The more frequently reported toxicities in the palbociclib arm as opposed to the placebo group included, leucopenia, neutropenia, and fatigue. There was a very rare incidence of febrile neutropenia, according to the study.

By Jeanette Smith
Edited By Leigh Haugh

Huffington Post–Over Weight Women Have Increased Risk for Breast Cancer After Menopause
Cancer Network–TDM-1 Better Than Trastuzumab in HER2,-HR-Positive Breast Cancer
OncLive–Palbociclib More Than Doubles PFS in Pretreated HR+/HER2 – Breast Cancer

Photos courtesy of:
Second photo courtesy of–Aristocrat’s Flickr Page – Creative Commons License
Top photo courtesy of–mimitalks, married, under grace’s Flickr Page – Creative Commons License
Third photo courtesy of–mimitalks, married, under grace 2’s Flickr Page – Creative Commons License
Featured image courtesy of–Susan G. Komen’s Flickr Page – Creative Commons License

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