Breast Cancer

How broccoli protects against breast cancer

An  article published in the December, 2008 issue of the journal Carcinogenesis <>  explains how broccoli and  other cruciferous vegetables protect against cancer of the breast.  Increased intake of cruciferous vegetables, which also include  cauliflower, Brussels sprouts and cabbage, has been associated with a  lower risk of breast and other cancers, yet their mechanism of action  against the disease has not been thoroughly explored.

Researchers  at the University of California Santa Barbara laboratories of Professors  Leslie Wilson and Mary Ann Jordan studied the effects of sulforaphane, one  of a group of cruciferous vegetable compounds known as isothiocyanates, on  cultured human breast cancer cells. They found that sulforaphane inhibits  tumor cell proliferation in a manner similar to that of taxol and  vincristine, which are powerful anticancer drugs. The drugs help prevent  cell division during a process known as mitosis, in which duplicated DNA  in the cells’ chromosomes is distributed to two daughter cells. The  chromosomes are separated with the assistance of tube-like structures  known as microtubules, whose function is interfered with by taxane and  vinca alkaloid drugs. Sulforaphane similarly interferes with microtubule  function during mitosis, but its action is weaker than the pharmaceutical  agents, lessening the potential for toxicity.

"Breast  cancer, the second leading cause of cancer deaths in women, can be  protected against by eating cruciferous vegetables such as cabbage and  near relatives of cabbage such as broccoli and cauliflower," first author  and UC Santa Barbara graduate student Olga Azarenko commented. "These  vegetables contain compounds called isothiocyanates which we believe to be  responsible for the cancer-preventive and anticarcinogenic activities in  these vegetables. Broccoli and broccoli sprouts have the highest amount of  the isothiocyanates.”

"Our  paper focuses on the anticancer activity of one of these compounds, called  sulforaphane, or SFN," Dr Azarenko stated. "It has already been shown to  reduce the incidence and rate of chemically induced mammary tumors in  animals. It inhibits the growth of cultured human breast cancer cells,  leading to cell death."

"Sulforaphane  may be an effective cancer preventive agent because it inhibits the  proliferation and kills precancerous cells," concurred Dr Wilson, who is a  professor of biochemistry and pharmacology at UC Santa Barbara. The  compound also has potential as an additive therapy to antimitotic drugs to  enhance their effects without increasing toxicity.

Breast cancer genes raise prostate risks in men

Thursday, 29 January 2009 00:00 WASHINGTON - The so-called breast cancer genes BRCA1 and BRCA2 can raise the risk that a man who develops prostate cancer will get an aggressive form of the disease, U.S. researchers reported on Thursday. Certain mutations in the genes indicated a man was at risk of more aggressive cancer and should be treated right away, the team at the Albert Einstein College of Medicine of Yeshiva University said. Their study of 2,000 Jewish men shows the gene mutation, more common among Jews of European descent, might help show which men have a slow-growing tumor that may not need immediate treatment.


The so-called breast cancer genes BRCA1 and BRCA2 can raise the risk that a man who develops prostate cancer will get an aggressive form of the disease, U.S. researchers reported on Thursday.

Certain mutations in the genes indicated a man was at risk of more aggressive cancer and should be treated right away, the team at the Albert Einstein College of Medicine of Yeshiva University said.

Their study of 2,000 Jewish men shows the gene mutation, more common among Jews of European descent, might help show which men have a slow-growing tumor that may not need immediate treatment. “One of the biggest problems with early-stage prostate cancer is being able to distinguish between tumors with the potential to become aggressive and those that may persist for many years without enlarging or spreading,” said Dr. Robert Burk, who led the study.

He said Ashkenazi Jewish men diagnosed with early-stage prostate cancer might want to consider getting tested for the mutations in BRCA2 and BRCA1.

“Our large study shows conclusively that prostate cancer patients with either the BRCA2 gene mutation or the BRCA1-185delAG mutation are more susceptible to aggressive cancers than people without that mutation,” Burk added in a statement.

For their study, Burk and colleagues tested 979 men with prostate cancer and 1,251 men without it for BRCA1 and BRCA2, both rare genetic mutations known in women to raise the risk of breast and ovarian cancers considerably. Men with any one of three mutations in the two genes were not any more likely to be in the prostate cancer group. But, if they did have one, their cancer was much more likely to be of an aggressive type, Burk’s team reported in Clinical Cancer Research.

Prostate cancer is the second-leading cancer killer of men, killing 221,000 every year globally, with 679,000 new cases diagnosed.

It is easily cured in early stages with surgery or radiation and some men have such slow-growing tumors that they are advised not to have any treatment at all. But distinguishing between the two is tricky and doctors welcome any new tools they can use to guide them.

Daily aspirin reduces estrogen receptor positive breast cancer risk

  A  report published online on April 30, 2008 in the journal Breast Cancer Research   concluded that the use of  aspirin on a daily basis reduced the risk of estrogen receptor-positive  breast cancer, which makes up 75 percent of breast cancer cases. These  cancers have receptors on their surface for female hormone estrogen, which  fuels the tumors’ growth.

Gretchen  L. Gierach and her colleagues at the National Cancer Institute evaluated  data from 127,383 women aged 51 to 72 who were enrolled in the National  Institutes of Health-AARP Diet and Health Study, which examined the  relationship between diet, health-related behaviors and cancer.  Questionnaires completed upon enrollment between1995 and 1996 provided  information on diet history, demographic characteristics and other data. A  second questionnaire completed between 1996 and 1997 collected information  concerning medication use, including aspirin and nonaspirin nonsteroidal  anti-inflammatory drugs (NSAIDs). Breast cancer cases were identified  through cancer registry information through the end of 2003.

Over  the period examined, 4,501 women developed breast cancer. Of the invasive  breast cancer cases for which estrogen receptor status was available,  1,439 were estrogen receptor positive and 280 estrogen receptor negative.  Although NSAID use was not linked to a reduction in overall breast cancer  risk, women who reported daily aspirin use had a 16 percent lower risk of  estrogen receptor positive breast cancer than women who did not use the  drug. There was also a significant reduction in risk in breast cancer in  situ (localized cancer) among daily aspirin users.

The  study is one of the largest to date to evaluate the association between  the type of NSAID used and breast cancer risk by tumor characteristics.  The authors remark that the association of a reduction in estrogen  receptor-positive breast cancer with aspirin is consistent with aspirin’s  ability to permanently inactivate cyclooxygenase-2 (COX-2), which  suppresses estrogen synthesis by decreasing aromatase activity, among  other pathways of risk reduction. COX-2 is expressed both in situ and  invasive breast cancer, and its upregulation may be an early event in  carcinogenesis.

“Our  results provide support for further evaluating relationships in  prospective studies with well-defined measures of NSAID use by NSAID type,  by breast cancer stage, and by estrogen receptor status,” the authors  conclude.

Impact of Off Label Chemotherapy in Breast Cancer

M. D. Anderson Study First to Evaluate Prevalence, Impact of Off Label Chemotherapy in Breast CancerDrugs not always approved for reimbursement, despite shown to be efficacious

[ABSTRACT #1016]

ORLANDO – At some point during their care, more than one-third of metastatic breast cancer patients receive chemotherapy off label, the legal use of FDA-approved drugs in a different indication than for which they were approved, according to researchers at The University of Texas M. D. Anderson Cancer Center.

The study, to be presented in a poster discussion at the American Society of Clinical Oncology’s upcoming annual meeting, is the first to evaluate the prevalence and impact of off label therapies in breast cancer. According to Sharon Giordano, M.D., associate professor in M. D. Anderson’s Department of Breast Medical Oncology, the only other study looking at off label chemotherapies and their prevalence was conducted almost 20 years ago by the US General Accounting Office, and evaluated their use in cancer overall.

After rigorous clinical trials for safety and efficacy, drugs are approved by the FDA for use in a specific population and limited indication – metastatic breast cancer patients, in the front line setting, for example. However, once a drug is approved, physicians can prescribe it as they find appropriate.

While the use of chemotherapies off their FDA label is known to be common practice in the management of breast and other cancers, before now, there’s been little research to quantify the use of off label chemotherapy agents and their impact, said Giordano.

“Off labels run a dramatic spectrum – sometimes there’s strong evidence that the use of a particular drug in a specific setting is efficacious, but perhaps the drug company has not gone through the regulatory process of getting an indication. In contrast, some uses of off label drugs that are completely inappropriate and may put patients at risk,” explained Giordano, the study’s senior author.

The issue also is controversial because off label therapies are often not approved by Medicare and/or insurance companies, even when shown to be effective in clinical trials, said Giordano.

Giordano and her researchers used the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database, the premier population-based cancer registry representing 26 percent of the country’s population, to identify 2,082 women older than 65 diagnosed with metastatic breast cancer between 1991 and 2002. To evaluate the appropriateness of off label drugs prescribed, the researchers referenced a specific drug compendium, DRUGDEX.

The researchers found that 34.9 percent of the women were treated with off label chemotherapy at some point during their care. Of the 36 chemotherapy agents identified to treat these patients, 8 (22 percent) were FDA-approved for use in breast cancer. However, while 71 percent of the drugs used off label lacked supporting evidence for their use in breast cancer, these drugs were used in a relatively small number of patients – 6.7 percent of the women received off label drugs considered medically inappropriate for use in treatment of breast cancer.

The most common off label chemotherapies noted were vinorelbine (approved for lung cancer), and gemcitabine (approved for pancreatic cancer), with 16 percent and 8.4 percent of the patients receiving these agents, respectively. Both of these agents have shown efficacy in the treatment of metastatic breast cancer, said Giordano. Gemcitabine has been subsequently approved for breast cancer when given in combination with paclitaxel.

As the study focused on women older than 65 - and physicians tend to be more conservative in treating their older patients – Giordano feels that her findings may underestimate the use of off labels across the breast cancer treatment pendulum.

Although commonly used in breast cancer, off label drugs are a greater necessity, and present a bigger dilemma for rare cancers, said Giordano. While perhaps a drug is shown to be efficacious in smaller Phase II clinical trials, conducting large Phase III trials in rare tumors is much more difficult, and thereby of less cost-benefit to drug companies. As a follow-up to this study, Giordano plans to look at off label use across a variety of tumor types and stages of cancer. She also intends to review their use in younger breast cancer patients.

“I think our study represents a very difficult and relevant policy issue that will soon need to be addressed. For all cancers, it’s important to try and strike a balance between having insurance coverage and access to appropriate, potentially life-saving off label drugs and protecting patients from being treated with therapies that haven’t been shown to be efficacious,” said Giordano.

In addition to Giordano, other authors on the all M. D. Anderson study include: Gabriel Hortobagyi, M.D., professor and chair of the Department of Breast Medical Oncology: Shenying Fang, also of the Department of Breast Medical Oncology; Wendy Dean-Colomb, M.D., fellow and the study’s first author; Laura Michaud, Ph.D., PharmD; and Wendy Smith, PharmD, both of the Department of Pharmacy Clinical Programs.

Sharon Giordano, M.D.


Contact: Laura Sussman 713-745-2457

Diet and Breast Cancer

"Prudent" diet linked to lower breast cancer risk 10-01-09

NEW YORK (Reuters Health) – A diet rich in fruits, vegetables and whole grains, and low in sweets and processed meats, may help lower the risk of breast cancer in some African-American women.

In a study of more than 50,000 African-American women, researchers found that thinner and younger women who ate a generally "prudent" diet were less likely to develop breast cancer than their counterparts who maintained a more Western-style diet.

There was no evidence that healthier eating lowered the risk among overweight women, or those past menopause. However, the prudent diet was linked to a generally lower risk of estrogen receptor-negative breast cancer -- an aggressive type of tumor that accounts for about one-third of breast cancers.

The prudent diet is one rich in whole grains, fruits, vegetables and fish, and lower in red and processed meats, sweets and starchy carbohydrates, like white bread. The opposite pattern is true of the so-called Western-style diet.

The new findings, published in the American Journal of Clinical Nutrition, add to the understanding of how these diet patterns may affect breast cancer risk in different groups of women.

Past studies have suggested that the prudent diet may help lower breast cancer risk in at least some women. But there has been a lack of studies focused on black women, according to the researchers on the new work, led by Tanya Agurs-Collins of the U.S. National Cancer Institute.

Their findings are based on a long-term study launched in 1995 that is following the health and lifestyle habits of 50,778 black women from across the U.S. Between 1995 and 2007, 1,094 of those women were diagnosed with breast cancer.

The researchers found no strong evidence that the prudent diet lowered breast cancer risk for the study group as a whole.

However, when they focused on normal-weight women, they found that as scores on the prudent-diet scale rose, the risk of developing breast cancer declined. The 20 percent of women with the most prudent diets were about one-third less likely to develop the disease than their counterparts with the least prudent eating habits.

Similarly, the healthier diet was linked to a lower cancer risk among premenopausal women. Those with the most prudent diets were 30 percent less likely to be diagnosed with breast cancer.

Other studies, according to the researchers, have found that a healthy diet may lower breast cancer risk in normal-weight women, but not those who are overweight.

The reasons are unknown, but taken together, the researchers write, these studies suggest that the protective effect of a prudent diet may be "largely among thinner women."

The issue of age appears more complicated, however. Agurs-Collins and her colleagues point out that some studies have linked the prudent diet to a lower breast cancer risk in postmenopausal women.

As for why the diet might be protective against estrogen receptor-negative tumors, in particular, the reasons are not clear. But the findings may be particularly important for younger African-American women, as they are more likely than their white counterparts to develop this type of tumor, the researchers point out.

Whatever the effects on breast cancer, though, the prudent diet is one that is recommended for better overall health -- including a lower risk of heart disease, the number-one killer of U.S. women.

SOURCE: American Journal of Clinical Nutrition, September 2009.