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5/31/2010

A first-of-its-kind vaccine to prevent breast cancer has shown overwhelmingly favorable results in animal models, according to a study by researchers at Cleveland Clinic’s Lerner Research Institute.

The researchers found that a single vaccination with the antigen ?-lactalbumin prevents breast cancer tumors from forming in mice, while also inhibiting the growth of already existing tumors. Enrollment in human trials could begin next year. If successful, it would be the first vaccine to prevent breast cancer.

The research is published online at http://www.nature.com/naturemedicine and will be published in the June 10 issue of Nature Medicine.

“We believe that this vaccine will someday be used to prevent breast cancer in adult women in the same way that vaccines have prevented many childhood diseases,” said Vincent Tuohy, Ph.D., the study’s principal investigator and an immunologist in Cleveland Clinic’s Lerner Research Institute.“If it works in humans the way it works in mice, this will be monumental. We could eliminate breast cancer.”

In the study, genetically cancer-prone mice were vaccinated – half with a vaccine containing ?-lactalbumin and half with a vaccine that did not contain the antigen. None of the mice vaccinated with ?-lactalbumin developed breast cancer, while all of the other mice did.

The U.S. Food and Drug Administration has approved two cancer-prevention vaccines, one against cervical cancer and one against liver cancer. However, these vaccines target viruses – the human papillomavirus (HPV) and the Hepatitis B virus (HBV) – not cancer formation.

In terms of developing a preventive vaccine, cancer presents a quandary not posed by viruses. While viruses are recognized as foreign invaders by the immune system, cancer is not. Rather, cancer is an over-development of the body’s own cells. Trying to vaccinate against this cell over-growth would effectively be vaccinating against the recipient’s own body, destroying healthy tissue.

The key, Dr. Tuohy said, is to find a target within the tumor that is not typically found in a healthy person. In the case of breast cancer, Dr. Tuohy and his research team targeted ?-lactalbumin – a protein that is found in the majority of breast cancers, but is not found in healthy women, except during lactation. Therefore, the vaccine can rev up a woman’s immune system to target ?-lactalbumin – thus stopping tumor formation – without damaging healthy breast tissue. The strategy would be to vaccinate women over 40 – when breast cancer risk begins to increase and pregnancy becomes less likely. (If a woman would become pregnant after being vaccinated, she would experience breast soreness and would likely have to choose not to breast feed.) For younger women with a heightened risk of breast cancer, the vaccine may be an option to consider instead of prophylactic mastectomy.

“Most attempts at cancer vaccines have targeted viruses, or cancers that have already developed,” said Joseph Crowe, M.D., Director of the Breast Center at Cleveland Clinic. “Dr. Tuohy is not a breast cancer researcher, he’s an immunologist, so his approach is completely different – attacking the tumor before it can develop. It’s a simple concept, yet one that has not been explored until now.”

Dr. Tuohy believes that the findings of this study go beyond breast cancer, providing insight into the development of vaccines to prevent other types of cancer. The results show that the antigen used in a cancer vaccine must meet several criteria: it must be over-expressed in the majority of targeted tumors; and it must not be found in normal tissue, except under specific, avoidable conditions (such as lactation).

Am J Clin Nutr. 2009 Sep;90(3):664-71. Epub 2009 Jul 22.

Dietary fiber intake and risk of breast cancer in postmenopausal women: the National Institutes of Health-AARP Diet and Health Study.

Park Y, Brinton LA, Subar AF, Hollenbeck A, Schatzkin A.

Divisions of Cancer Epidemiology and Genetics and Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA. parkyik@mail.nih.gov

BACKGROUND: Although dietary fiber has been hypothesized to lower risk of breast cancer by modulating estrogen metabolism, the association between dietary fiber intake and risk of breast cancer by hormone receptor status is unclear. OBJECTIVE: The objective was to examine the relation of dietary fiber intake to breast cancer by hormone receptor status and histologic type among postmenopausal women in the National Institutes of Health-AARP Diet and Health Study (n = 185,598; mean age: 62 y). DESIGN: Dietary intakes were assessed with a food-frequency questionnaire. Incident breast cancer cases were identified through linkage with state cancer registries. Cox proportional hazard models were used to estimate relative risks (RRs) and 2-sided 95% CIs. RESULTS: During an average of 7 y of follow-up, 5461 breast cancer cases were identified, of which 3341 cases had estrogen receptor (ER) and progesterone receptor (PR) status. Dietary fiber intake was inversely associated with breast cancer risk [RR for the highest quintile (Q5) compared with the lowest quintile (Q1): 0.87; 95% CI: 0.77, 0.98; P for trend: 0.02]. The inverse association appeared to be stronger for ER(-)/PR(-) tumors (RR(Q5vsQ1): 0.56; 95% CI: 0.35, 0.90; P for trend: 0.008; 366 cases) than for ER(+)/PR(+) tumors (RR(Q5vsQ1): 0.95; 95% CI: 0.76, 1.20; P for trend: 0.47; 1641 cases). The RR(Q5vsQ1) of lobular tumors was 0.66 (95% CI: 0.44, 0.97; P for trend: 0.04), and the RR(Q5vsQ1) of ductal tumors was 0.90 (95% CI: 0.77, 1.04; P for trend: 0.10). Fiber from grains, fruit, vegetables, and beans was not related to breast cancer. CONCLUSION: Our findings suggest that dietary fiber can play a role in preventing breast cancer through nonestrogen pathways among postmenopausal women.

Thu Sep 9 By Amy Norton

NEW YORK (Reuters Health) - In findings that could make broccoli and Brussels sprouts easier to swallow, early research suggests a chemical found in the vegetables may impede the spread of breast cancer cells.

Scientists found that the compound, called sulforaphane, hindered the growth of human breast cancer cells in the lab. It did so by apparently disrupting the action of protein 'microtubules' within the cells, which are vital for the success of cell division.

The findings are published in the Journal of Nutrition.

Past research has suggested a role for sulforaphane in preventing cancer, possibly due to its effects on detoxification enzymes that can defend against cancer-promoting substances. A study in rats showed that oral sulforaphane blocked the formation of breast tumors, and scientists have found that the chemical can push colon cancer cells to commit suicide.

This latest research suggests a new mechanism -- microtubule disruption -- by which sulforaphane may bestow anti-cancer benefits, according to study co-author Dr. Keith Singletary, a professor of nutrition at the University of Illinois at Urbana-Champaign.

What's "intriguing" about this finding, he told Reuters Health, is that certain cancer drugs work in a similar manner. It's possible that sulforaphane, perhaps in combination with other compounds or drugs, could eventually aid in the prevention or treatment of cancer, according to Singletary.

Whether a diet rich in broccoli and other sulforaphane-containing foods packs enough of the compound to lower cancer risk is unknown. Numerous studies in the general population have linked high vegetable and fruit intake to a lower risk of cancer, including breast cancer -- but zeroing in on which components of these foods may deserve the credit is a tough task.

Much remains to be learned about the chemicals in plant foods, Singletary noted, and scientists generally believe that it's important to get the full complement of nutrients and chemicals in these foods.

"Most people would recommend eating a variety of whole vegetables and fruits," he said.

SOURCE: Journal of Nutrition, September 2004. 

Menstruating women: Hormonal changes due to the menstrual cycle may make the breasts more lumpy or swollen. Women who are menstruating should perform breast self-exam from a few days to about a week after menstruation (period) has ended, when breasts are usually less tender or swollen.

Breast self-exams should be performed once each month beginning at age 20 and continue each month throughout a woman’s lifetime.

Women who are no longer menstruating: should do their BSE on the same day every month. Try to pick a day that is easy to remember, such as the first or fifteenth of every month, and make that the day each month for breast self-exam.

Women using oral contraceptives: are encouraged to do their BSE each month on the day they begin a new package of pills.

Breast Changes and Warning Signs To Watch for During Breast Self-Exam:

If any of these changes are noted, women should see their physicians as soon as possible for clinical evaluation. However, in the majority of cases (80%), breast lumps and changes are not cancer. Women should not allow their fear of breast cancer keep them from telling their physician or healthcare provider about a lump or change they have found.

Women should continue monthly breast self-examination (BSE) during pregnancy. Clinical breast examination by a healthcare professional should also be made on a monthly basis during pregnancy. It is especially important that clinical breast exam be performed during the first doctor visit of the pregnancy, before the breasts go through significant physiologic changes. Some changes or lumps are more difficult to evaluate once the breasts have enlarged and become more nodular. The main problem with breast cancer during pregnancy is a delay in diagnosis that results in women being diagnosed with breast cancer at a later, more advanced stage. Vigilant, monthly breast self-examination during pregnancy and afterwards during breast-feeding can help prevent delayed diagnosis of breast cancer and enables optimal treatment.

Normal, non-cancerous lumps such as cysts are usually soft, smooth and moveable

Suspicious lumps are usually firm, irregular in shape and fixed in place

Approximate percentage of breast cancers found in each area:

41% in the upper, outer quadrant

14% in the upper, inner quadrant

5% in the lower, inner quadrant

34% in the area behind the nipple

6% in the lower, outer quadrant