A secondary analysis of a large, multicenter clinical trial has shown that a diet loaded with fruits, vegetables and fiber and somewhat lower in fat compared to standard federal dietary recommendations cuts the risk of recurrence in a subgroup of early-stage breast cancer survivors – women who didn’t have hot flashes – by approximately 31 percent. These patients typically have higher recurrence and lower survival rates than breast cancer patients who have hot flashes. The study team, led by researchers at the Moores Cancer Center at the University of California, San Diego, along with six other sites, including the University of California, Davis, reported its results online December 15, 2008, in the Journal of Clinical Oncology.

The results come on the heels of a report last year on the findings of the original study, the Women's Healthy Eating and Living Trial (WHEL), which compared the effects of the two diets on cancer recurrence in more than 3,000 early-stage breast cancer survivors. That study showed no overall difference in recurrence among the two diet groups.

"Women with early stage breast cancer who have hot flashes have better survival and lower recurrence rates than women who don't have hot flashes," said Ellen B. Gold, Ph.D., professor and chair of the UC Davis Department of Public Health Sciences and first author of the study. "Our results suggest that a major change in diet may help overcome the difference in prognosis between women with and without hot flashes."

"Our interest in looking at this subgroup came because hot flashes are associated with lower circulating estrogen levels, while the absence of hot flashes is associated with higher estrogen levels. Reducing the effect of estrogen is a major treatment strategy in breast cancer," said the WHEL study principal investigator John P. Pierce, Ph.D., Sam M. Walton Professor for Cancer Prevention and director of Cancer Prevention and Control at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. "It appears that a dietary pattern high in fruits, vegetables and fiber, which has been shown to reduce circulating estrogen levels, may only be important among women with circulating estrogen levels above a certain threshold."

About 30 percent of the original group of 3,088 breast cancer survivors did not report hot flashes at study entry. The women had been randomly assigned to one of the two diets between 1995 and 2000 and were followed until 2006. About one-half (447) of the "no hot flashes" group were randomized to the special, "intervention" high-vegetable fruit diet while the other half (453) was given the generally recommended diet of five servings of fruits and vegetables a day. The team found that those on the intervention diet had a significantly lower rate of a second breast cancer event (16.1 percent) compared to those eating the government-recommended five-a-day dietary pattern (23.6 percent).

The dietary effect was even larger (a 47 percent lower risk) in women who had been through menopause.

According to Pierce, another possible mechanism has been proposed recently for why this diet may have affected only 30 percent of the WHEL study population. Women with estrogen receptor-positive cancers usually receive hormone therapy (tamoxifen or aromatase inhibitors) aimed at combating the effect of circulating estrogen. However, more than 30 percent of these women appear to have a gene-drug interaction that prevents them from getting an effective dose of this therapy.

"This hypothesis says that if the endocrine therapy is working, no further reduction in estrogen levels would be needed," said Pierce. "If your genes are preventing you from getting a therapeutic dose, then following this rigorous dietary pattern may reduce estrogen levels enough to reduce risk." Because this is speculation, he said, the research team will be using biological samples collected throughout the study to further investigate the mechanisms behind the study diet's protective effects.

Other co-authors include: Cheryl Rock, Ph.D., Barbara Parker, M.D., Lisa Madlensky, Ph.D., Loki Natarajan, Ph.D., Linda Wasserman, M.D., Vicky Jones, M.D., Gail Laughlin, Ph.D., Nazmus Saquib M.D., Ph.D., Sheila Kealey MPH, Shirley Flatt, Jennifer Emond and Minya Pu, UCSD; Joanne Mortimer, M.D., City of Hope; Marcia Stefanek, Ph.D., Stanford University; Bette Caan, Dr.P.H, Kaiser Permanente, Oakland, Cynthia Thomson, Ph.D., University of Arizona, Njeri Karanja, Ph.D., Kaiser Permanente, Portland, OR; Richard Hajek, Ph.D., M.D. Anderson Cancer Center.

About Breast Cancer

• Ductal carcinoma in situ (DCIS): This is the most common type of non-invasive breast cancer (85 - 90% of all cases). DCIS means that the cancer is only in the ducts. It has not spread through the walls of the ducts into the tissue of the breast. Nearly all women with cancer at this stage can be cured. Often the best way to find DCIS early is with a mammogram.
• Lobular carcinoma in situ (LCIS): This condition which occurs in approximately 8% of all cases, begins in the milk-making glands but does not go through the wall of the lobules. Although not a true cancer, having LCIS increases a woman's risk of getting cancer later. For this reason, it's important that women with LCIS to follow the screening guidelines for breast cancer.

• Inflammatory breast cancer (IBC): This uncommon type of invasive breast cancer accounts for about 1% to 3% of all breast cancers. Usually there is no single lump or tumor. Instead, inflammatory breast cancer (IBC) makes the skin of the breast look red and feel warm. It also gives the skin a thick, pitted appearance that looks a lot like an orange peel. Doctors now know that these changes are not caused by inflammation or infection, but by cancer cells blocking lymph vessels in the skin. The breast may become larger, firmer, tender, or itchy. IBC is often mistaken for an infection in its early stages. Because there is no defined lump, it may not appear on a mammogram, which may make it even harder to catch it early. It usually has a higher chance of spreading and a worse outlook than invasive ductal or lobular cancer.
• Paget's disease of the nipple. Paget's disease of the nipple or breast is a rare type of breast cancer, which can occur in women and men. It shows up in and around the nipple, and usually signals the presence of breast cancer beneath the skin. Most cases are found in menopausal women, but can also appear in women that are as young as 20.  Early stages symptoms include redness, scaly and flaky, and  mild irritation of  nipple skin. Advanced stages may include: tingling in nipple skin, very sensitive skin on the nipple, burning or painful nipple skin, ooze or bloody discharge from the nipple (not milk), itchiness that doesn't respond to creams, nipple retraction (pulls into the breast), scaly rash on areola skin, and/or breast lump beneath the affected skin.

• a lump or a thickening in the breast or in the armpit. Note Most breast lumps are benign (be-nine); that is, they are not cancer. Benign breast tumors are abnormal growths, but they do not spread outside of the breast and they are not life threatening. But some benign breast lumps can increase a woman's risk of getting breast cancer. Most lumps turn out to be caused by fibrocystic (fi-bro-sis-tik) changes. Cysts are fluid-filled sacs. Fibrosis is the formation of scar-like tissue. Such changes can cause breast swelling and pain. The breasts may feel lumpy, and sometimes there is a clear or slightly cloudy nipple discharge.
• a change of size or shape of the mature breast
• fluid (not milk) leaking from the nipple
• a change of size or shape of the nipple
• a change of color or texture of the nipple or the areola, or of the skin of the breast itself (dimples, puckers, rash)
• a discharge from the breast

About the Moores UCSD Cancer Center