3-D Mammography Imaging System Approved

The U.S. Food and Drug Administration today approved the Selenia Dimensions System, the first X-ray mammography device that provides three-dimensional (3-D) images of the breast for breast cancer screening and diagnosis.

A mammogram is a safe, low-dose X-ray of the breast that is the best tool for early detection of breast cancer. However, with the limitations of conventional two-dimensional (2-D) imaging, about 10 percent of women undergo additional testing after the initial screening exam for abnormalities that are later determined to be noncancerous. [Read more…]

Chemotherapy Drug Resistance Linked to Genetic Variant in Women with Breast Cancer

Researchers have found links between an individual’s genetics and their response to treatment with chemotherapy. The findings, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues, show how a genetic variant, located in the SOD2 gene, may affect how a person responds to the chemotherapy drug cyclophosphamide. Cyclophosphamide is used in the treatment of breast and other cancers.

The SOD2 gene produces a key protein that protects cells from damage by molecules known as reactive oxygen species, or free radicals. Reactive oxygen species are produced by normal cellular processes and the action of some chemotherapy drugs. The findings represent the first preliminary evidence pointing toward a mechanism and a potential biomarker for cyclophosphamide resistance in breast cancer patients. The study appeared online June 9, 2009, in Clinical Cancer Research.

“This study shows how, with the progress of individualized medicine, a diagnostic test may be developed that determines whether a patient has certain genetic variations that may modify the effect of certain chemotherapies,” said study author Sharon Glynn, Ph.D., of NCI’s Center for Cancer Research.

“In the future, such tests may be used to guide the treatment of patients with the SOD2 variation, ensuring that they receive a therapy that is more effective than cyclophosphamide-based therapies,” added senior author Stefan Ambs, Ph.D., also of the Center for Cancer Research.

Most genes in human cells are present in two copies — one inherited from the mother and the other inherited from the father. These gene copies can vary from one another. Some variations in genes play an important role in how a gene is expressed or how its protein product functions.

The variant identified by the researchers in the SOD2 gene affects both the structure and the function of the encoded protein, an enzyme known as manganese superoxide dismutase (MnSOD) and affects the ability of MnSOD to reach its proper location in the cell and its activity level. MnSOD normally functions inside cellular compartments known as mitochondria and helps protect cells from damage caused by reactive oxygen species formed during cellular metabolism. Excessive levels of reactive oxygen species can be toxic to cells. Indeed, some anticancer drugs depend on increased production of reactive oxygen species to kill cancer cells. Furthermore, some studies have indicated that, because MnSOD neutralizes reactive oxygen species, it can modify the effects of chemotherapy drugs. For example, in laboratory and animal models, increased activity of MnSOD protects cells against the toxic effects of doxorubicin, which is a widely used anticancer drug.

In the new study, the research team investigated whether the variation affected survival in two separate groups of women with breast cancer: 248 women in the United States and 340 women in Norway. Some of the women received chemotherapy, and some did not receive chemotherapy. The team first analyzed DNA from the women to determine their genotype, meaning which types of the SOD2 gene they had. The researchers found that, among patients who received chemotherapy, those who had one form had decreased survival and those with another form had the poorest survival. In contrast, the genotype of SOD2 did not affect survival among those who did not receive chemotherapy.

Next, the team looked at the relationship between SOD2 genotype and the type of chemotherapy the women received. The data were analyzed according to which of three types of commonly used chemotherapy drugs were administered: doxorubicin, 5-fluorouracil, or cyclophosphamide. Both doxorubicin and cyclophosphamide generate reactive oxygen species in cancer cells during treatment. The researchers determined that the presence of a particular variant was associated with decreased survival of patients treated with chemotherapy regimens that contained any of the three drugs. However, the most significant effects were found with the drug cyclophosphamide. Women with a distinct variant form of SOD2 and who received cyclophosphamide-containing chemotherapy had the poorest survival.

The research team says more work is necessary to confirm these findings and to examine the precise mechanism by which a genotype influences the response of cancer cells to cyclophosphamide. The team plans to examine the influence of several variations on the resistance to other chemotherapies.

Source: National Institutes of Health (NIH), 6/9/2009

Sports and Exercise Reduces Breast Cancer Rates

Women who actively participate in sports are 25% less likely to get breast cancer, though the benefits are not seen in obese women, and lean women see the lowest breast cancer rates.

The type of activity undertaken, at what time in life and the woman’s body mass index (BMI) will determine how protective the activity is against the disease.

The researchers reviewed the literature and analysed 62 studies looking at the impact of physical activity on breast cancer risk. They then examined the findings to find out how breast cancer risk appeared to be affected by type of activity, intensity of activity, when in life the activity was performed and other factors.

They found the most physically active women were least likely to get breast cancer. All types of activity reduced breast cancer risk but recreational activity reduced the risk more than physical activity undertaken as part of a job or looking after the house. Moderate and vigorous activity had equal benefits.

Women who had undertaken a lot of physical activity throughout their life had the lowest risk of breast cancer, and activity performed after the menopause had a greater effect than that performed earlier in life.

Physical activity reduced breast cancer risk in all women except the obese and had the greatest impact in lean women (BMI < 22kg/m2)

Women who were mothers, had no family history of breast cancer, were not white and had oestrogen receptor negative tumours also had a reduced risk of breast cancer.

The authors said the way in which physical activity protected against breast cancer was likely to be complex and may involve effects on sex hormones, insulin-related factors, the immune system and other hormone and cellular pathways.

Source: British Journal of Sports Medicine 2008; doi:10.1136/bjsm.2006.029132

Obese Women Experience More Aggresive Breast Cancer

Obese women with breast cancer have lower rates of survival, and suffer a more intense form of the disease, according to recently-published research.

"The more obese a patient is, the more aggressive the disease," said Massimo Cristofanilli, MD, associate professor of medicine in the Department of Breast Medical Oncology at The University of Texas M.D. Anderson Cancer Center. "We are learning that the fat tissue may increase inflammation that leads to more aggressive disease."

606 women with breast cancer were observed by Cristofanilli and colleagues, and classified by body mass index into three groups—normal/underweight (24.9 or below), overweight (at least 25 but less than 30), or obese (more than 30). At five years, overall survival was 56.8 percent among obese women, 56.3 percent among overweight women and 67.4 percent among normal weight women. The 10-year survival rate was 42.7 percent among obese women, 41.8 percent among overweight women and 56.5 percent among normal weight women. Researchers found that the rate of inflammatory breast cancer was 45% among obese women, compared with 30% in overweight women, and 15% in women with normal weight.

Obese or overweight women also displayed a higher risk of breast cancer recurrence. Obese women (50.8%) reported a recurrence after 5 years, compared with normal weight women (38.5%). After 10 years, the rate of recurrence was 58% in obese women and 45.4% in women with normal weight.

"Obesity goes far beyond just how a person looks or any physical strain from carrying around extra weight. Particular attention should be paid to our overweight patients," Cristofanilli said.

Drugs commonly used to treat cancer patients, such as tamoxifen, said Dr. Cristofanilli tend to increase weight gain during treatment – an effect physicians should note carefully. "We have actually become quite good at managing acute side effects such as nausea in our chemotherapy patients and it goes away within a couple of days," Cristofanilli said. "Following the nausea, our patients tend to overeat, which further increases their risk of weight gain. We need to implement lifestyle modifications interventions and develop better methods to follow these patients closely."

Clinical Cancer Research, March 15, 2008

Increased Risk of Breast Cancer Recurrence Tied To High Levels of Estrogen

Women whose breast cancer returned after treatment had almost twice as much estrogen in their blood than did women who remained cancer-free, according to a newly published study.

The study’s lead author, Cheryl L. Rock, Ph.D., a professor in the Department of Family and Preventive Medicine at the University of California, San Diego, said that high levels of estrogen—which lead to the initial development of breast cancer—could be associated with an increased risk of recurring cancer.

"While this makes sense, there have been only a few small studies that have looked at the link between sex hormones in the blood and cancer recurrence," she said. "This is the largest study to date and the only one to have included women taking agents such as tamoxifen to reduce estrogen’s effect on cancer growth."

"What the results mean for women who have already been treated for breast cancer is that they should do as much as they can to reduce estrogen in their blood, such as exercising frequently and keeping weight down," she added. "Taking anti-estrogen drugs like tamoxifen may not completely wipe out the hormone’s effect in women who have high levels of estrogen."

The Women’s Healthy Eating and Living Study (WHEL) provided participants for the breast cancer study, a dietary intervention trial that monitored 3,088 women treated for breast cancer but cancer-free when recruited for the study. Subjects were placed in two groups—one that ate a " normal" healthy diet, one that ate extremely large amounts of fruits, fiber and vegetables. After 7 years, participants were checked for breast cancer, which was about the same for each group. Researchers interpreted the findings to mean that a normal diet that incorporates the U.S. Food and Drug Administration guidelines for recommended amounts of fruits and vegetables is sufficient.

In the current study, 153 WHEL participants whose cancer had recurred were matched with 153 participants who remained cancer-free. These pairs were alike in terms of tumor type, body size, age, ethnicity, use of chemotherapy and other variables. Two-thirds of the participants were using tamoxifen, Rock said.

When they enrolled, researchers tested the women’s blood for concentrations of the steroid hormones estradiol (the primary human estrogen) and testosterone. They analyzed different forms of estradiol and testosterone in the blood, such as how much was bound to transport proteins (such as to the sex hormone binding globulin, or SHBG) and how much was "free" circulating and able to enter a cell.

The study was published in the March issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.

FDA Approves Bristol-Meyers Squibb’s Drug Ixempra for Breast Cancer Treatment

The U.S. Food and Drug Administration has approved Ixempra (ixabepilone), a new anti-cancer treatment, for use in patients with metastatic or locally advanced breast cancer who have not responded to certain other cancer drugs.

Ixempra is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

"This approval is important because it provides certain patients with a new chemotherapy option in instances where other drugs have failed," said Douglas C. Throckmorton, M.D., deputy director of the FDA’s Center for Drug Evaluation and Research.

The FDA evaluated Ixempra under priority review, completing its assessment of the drug’s safety and effectiveness in six months.

Ixempra was approved for use in combination with another cancer drug, capecitabine, in patients who no longer benefit from two other chemotherapy treatments. These prior treatments included an anthracycline (such as doxorubicin or epirubicin) and a taxane (such as paclitaxel or docetaxel).

Ixempra was also approved for use alone in patients who no longer benefit from an anthracycline, a taxane and capecitabine.

According to the American Cancer Society, about 180,000 new cases of breast cancer are diagnosed each year in the United States. Metastatic breast cancer is the most advanced stage of breast cancer and has the potential to spread to almost any region of the body.

Ixempra has been shown to bind to cancer cell microtubules, which are structures within cells that help to support and shape them. Microtubules also play a role in cell division.

The safety and efficacy of Ixempra in combination with capecitabine were evaluated in 752 patients in a randomized clinical trial comparing the combination to capecitabine alone. This combination therapy demonstrated improvements in delaying cancer progression or death compared to capecitabine alone.

The safety and efficacy of Ixempra administered alone were evaluated in a study of 126 patients. Clinically significant tumor shrinkage occurred in 12 percent of the patients.

Ixempra’s significant side effects included peripheral neuropathy (numbness, tingling or burning in the hands or feet) and bone marrow suppression. Other commonly observed toxicities included constipation, nausea, vomiting, muscle paint, joint pain, fatigue and general weakness.

Women taking Ixempra should avoid taking drugs that are strong inhibitors of CYP3A4, one of the enzymes that metabolizes Ixempra.

Ixempra should not be taken by women who have had severe allergic reactions to drugs that contain Cremophor or its derivatives, or by women who have baseline bone marrow suppression determined by low white blood cell or platelet count.

The combination of Ixempra and capecitabine should not be given to patients with moderate or severe liver impairment due to the increased risk of toxicity and death.

Ixempra is administered by intravenous infusion. It is distributed by Bristol-Meyers Squibb Company, Princeton, New Jersey.

Source: FDA (October 22, 2007)

Three Alcohol Drinks Per Day May Significantly Increase Breast Cancer Risk

It isn’t the type of alcohol but the quantity which increases a woman’s risk of contracting breast cancer.

In fact, the increased breast cancer risk from drinking three or more alcoholic drinks a day is similar to the increased breast cancer risk from smoking a pack of cigarettes or more a day, according to Kaiser Permanente researchers Yan Li, MD, PhD and Arthur Klatsky, MD.

"Population studies have consistently linked drinking alcohol to an increased risk of female breast cancer, but until now there has been little data, most of it conflicting, about an independent role played by the choice of beverage type," said Klatsky, who is presentied these findings on Sept. 27 at the European Cancer Conference (ECCO 14) in Barcelona, Spain.

The study found there was no difference between wine, beer or spirits in the risk of developing breast cancer. Even when wine was divided into red and white, there was no difference. However, when researchers looked at the relationship between breast cancer risk and total alcohol intake, they found that women who drank between one and two alcoholic drinks per day increased their risk of breast cancer by 10 percent compared with light drinkers who drank less than one drink a day. The risk of breast cancer increased by 30 percent in women who drank more than three drinks a day.

"A 30 percent increased risk is not trivial. To put it into context, it is not much different from the increased risk associated with women taking estrogenic hormones. Incidentally, in previous research completed at Kaiser Permanente, we have found that smoking a pack of cigarettes or more per day is related to a similar (30 percent) increased risk of breast cancer," Klatsky said.

Although breast cancer incidence varies between populations and only a small proportion of women are heavy drinkers, Dr Klatsky said that a 30 percent increase in the relative risk of breast cancer from heavy drinking might translate into approximately an extra 5 percent of all women developing breast cancer as a result of their habit.

"Klatsky said that all medical advice needed to be personalized to the individual. "Our findings provide more evidence for why heavy drinkers should quit or cut down."

Source: Kaiser

New Breast Cancer Gene HMMR Found

Researchers have found a new gene called HMMR that, when mutated, may lead to a significantly greater chance of developing breast cancer. The study was a collaboration of international researchers from Spain, Israel, and several U.S. organizations.

The HMMR gene is mutated in about 10% of the population, while two other genes related to breast cancer, BRCA1 and CRCA2, are mutated in only about 0.3% of the popuation. According to the study’s authors, it’s important to identify more common breast cancer-related genes so that targeting the gene for early detection will have a greater impact.

The method of identifying the HMMR gene began with computer modeling to identify genes that impact cancer development and to see how they interact with other genes. Starting with four known breast cancer-related genes (BRCA1, BRCA2, ATM and CHEK2), researchers then showed that alterations of either BRCA1 or HMMR can lead to genetic instability and interfere with cell division.

To specifically understand whether variations in HMMR increased breast cancer risk, 923 women with breast cancer and similar women without breast cancer were analyzed in a study led by Gadi Rennert, M.D., director of the CHS National Cancer Control Center in Haifa, Israel. The results indicated that women in the study under 40 years of age with the HMMR variant (even after accounting for mutations in the BRCA1 or BRCA2 genes), had a 2.7 times greater risk of developing breast cancer than women without the variation.

The study was conducted among a population of Ashkenazi Jewish women, who have a higher risk of breast cancer than other groups.

The findings were verified in two other studies conducted in New York–one among another group of Ashkenazi Jewish women with a family history of breast cancer but no identified BRCA1 or BRCA2 mutations, and a third study of Jewish women with and without breast cancer in New York. Overall, 2,475 women with breast cancer and 1,918 healthy women were studied in Israel and New York.

The findings indicated that incidence of breast cancer was 23% higher in women who had one copy of the genetic variant, and 46% higher in women who had two copies of the variant. Researchers also concluded that HMMR may be associated with early-onset breast cancer, as the women with the HMMR variant were diagnosed about one year earlier than the control group.

"Identifying genes involved in cancer in the general population is important, because not all of the causes of breast cancer have been found. Through discoveries such as this, someday we might be able to more precisely estimate a person’s risk of cancer based on their genes," says study author Laura Rozek, Ph.D., a postdoctoral research fellow at the University of Medical School.

The study was funded by the National Cancer Institute, the National Institutes of Health, the Breast Cancer Research Foundation, the Niehaus, Southworth, Weissenbach Foundation, and the Koodish Foundation.

Sources: Nature Genetics, doi:10.1038/ngxxxx and University of Michigan

Pregnancy After Breast Cancer

While many women who go through breast cancer do so in their 50’s and are no longer considering childbirth, women who are treated for breast cancer at a younger age are often left wondering whether or not they will be able to have children afterwards.

Breast cancer treatments often involve chemotherapy regimens that can affect ovarian function, but according to Daniel F. Hayes, an M.D. and clinical director of the breast cancer oncology program at the University of Michigan, many women can still safely conceive after breast cancer treatments.

Fertility is certainly a concern for women undergoing breast cancer treatment and Dr. Hayes points out that fertility is definitely something that should be discussed before treatment. "That discussion is going to be specific for each patient," he notes, "because it depends how old she is, whether she should get chemotherapy, what kind of chemotherapy, and whether she cares about maintaining fertility."

Ovarian function can be affected by multiple factors in breast cancer treatment—particularly chemotherapy. While most chemotherapies negatively affect ovarian function, younger women have a better chance of regaining their periods after treatment than their older counterparts who may be closer to menopause.

Other therapies that affect fertility are the newer hormone-based therapies, which are often given for up to five years. To become pregnant, women would have to stop taking the hormone therapy for a period of time before conception. Dr. Hayes discourages this course however, because, he says, the benefits of the therapy are so great.

 Studies have shown that there should be little worry that breast cancer treatment therapies have an adverse effect on the newborn children. The risk of birth defects or miscarriages was not shown to be elevated among women who have undergone chemotherapy.

Some Breast Cancer Facts

  • Number of American breast cancer diagnosis in 2007: 180,510
  • U.S. deaths from breast cancer in 2007: 40,910
  • Breast cancer is the #3 leading cause of female deaths in the United States.
  • With early detection, breast cancer can be cured in 80 percent of women.
  • It is recommended that women over 50 get a mammogram every 12 months.
  • Never ignore a lump or change in the look or feel of your breast.

Decrease in Hormone Therapies Linked to Decline in Breast Cancer

Researchers claim that an analysis of patients’ treatment records at a large HMO indicate that reduced use of hormone replacement therapy (HRT) may be the cause behind declining breast cancer rates.
They pointed out that, as some studies suggest, this decline is not due to reduced use of mammography.

The research indicates that one of the main causes of the decline is due to the reduction in post menopausal hormone therapy in 2003, in response to results of Women’s Health Initiative that linked breast cancer to hormone replacement therapy.

Growth of small tumors slows down when hormone replacement therapy is discontinued delaying discovery by almost two years. With the number of post menopausal estrogen and progestin prescriptions reduced to almost half, cancer rates have dropped by 7% in the year 2003.