Breast Cancer Risk Higher If Estrogen Or Testosterone Levels Higher

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The risk of breast cancer is greater if levels of hormones estrogen or testosterone are higher in post-menopausal women, researchers from Brigham and Women's Hospital reported in Breast Cancer Research, an open-access BioMed Central journal. The researchers examined six different growth and sex hormones and discovered that higher levels raised breast cancer risk by 16% for each one.
Dr Shelley Tworoger and team examined blood samples of nurses up to nine years before their breast cancer status was recorded. They matched post-menopausal females who had been diagnosed with breast cancer with two controls of the same age.
The following hormones were individually linked to a 50% to 200% rise in breast cancer risk:

• Estrone - one of several natural estrogens.
• Estradiol - one of several natural estrogens.
• Testosterone - steroid hormone from the androgen group. Secreted in the testes of males and ovaries of females.
• Androstenedione - a 19-carbon steroid hormone. An intermediate step in the biochemical pathway that produces testosterone, estrone and estradiol.
• DHEA (Dehydroepiandrosterone) - a 19-carbon endogenous (originates from within the organism) steroid hormone. The most abundant circulating steroid in humans.
• DHEA-sulfate - a metabolite of of DHEA.

Breast cancer risk increases with the number of high level hormones

The higher the number of hormones at elevated levels, the higher the breast cancer risk, the scientists found. For example, a woman with one elevated hormone may have a 10% higher risk when compared to those with normal levels, while women with five or six hormones with elevated levels would have double (100% higher) the risk. For those with seven or eight hormones at high levels, there can be triple the risk.
The risk was a little higher for females with estrogen receptor (ER) positive disease.
Dr Shelley Tworoger said:

"Elevated estrogens had the biggest effect on risk, especially for ER positive cancer. However, androgens, and prolactin also contribute to increasing risk of breast cancer.
These hormones are known to stimulate the growth of breast cancer cells in the lab and, while androgens can be converted to estrogen in the body, these hormones have also been found to stimulate cancer cell growth in the absence of ER.

Our results suggest that models used to assess breast cancer risk could be improved by taking into account multiple sex hormone and growth hormone levels."

Written by Christian Nrodqvist

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False Positive Mammograms Affect Most Women After A Decade

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A new investigation of national Breast Cancer Surveillance Consortium data in the Annals of Internal Medicine reveals that, in one decade of yearly mammograms, over half of women without cancer will be called back for further testing, and approximately 1 in 12 women will be referred for a biopsy.
Investigation leader Rebecca Hubbard, PhD, an assistant researcher at Group Health Research Institute explained:

"We conducted this study to help women know what to expect when they get regular screening mammograms over the course of many years. We hope that if women know what to expect with screening, they'll feel less anxiety if - or when - they are called back for more testing. In the vast majority of cases, this does not mean they have cancer. When a woman without breast cancer is called back after screening mammography for extra testing, she has a "false positive."

We wanted to understand better how likely false-positive test results are when women receive annual screening mammograms compared to every other year - and starting at age 50 compared to age 40."

Hubbard and her team analyzed data from over 169,000 women who were aged between 40 to 59 years across seven regions in the U.S..
According to Hubbard, women's chances of having a false positive over the course of a decade was reduced from 61% to 42% when they were screen every other year, instead of annually. The probability of false positives was cut in half when women had previous mammograms available for comparison. Hubbard advises that women who don't return to the same facility where they had their previous mammogram, should arrange ahead of time for their previous mammograms to be sent to the new mammography facility.
Hubbard continued:

"We found that women in their 40s and 50s had similar risks of having false positive during 10 years of screening. But over the course of a lifetime, starting screening at age 40 would make a women more likely to have a false positives than if she had started at age 50, because of that extra decade of screening."

Their results revealed that women who were diagnosed with cancer from screening every other year were not considerably more likely to be diagnosed with late-stage cancer, compared to women who were screen annually. Hubbard explained: "Women should talk with their doctors to make informed decisions about how often is best for them to get screening - and when to start."
Mammography is the only screening test to reduce the risk of a women dying of breast cancer that has been verified in clinical trials. For women who receive a false-positive it can be an extremely stressful experience, and may prevent women from getting regular screening.
In the same issue of Annals, an associated Breast Cancer Surveillance Consortium study led by Karla Kerlikowske, MD, of the University of California, San Francisco, is the first to examine the accuracy of digital mammography in comparison to film mammography in U.S. community practice. Newer digital mammography has been replacing older film mammography over the past few years.
The investigators, including Dr. Hubbard, discovered that both digital and film mammograms performed similarly for those aged between 50 to 79 years for detecting cancer. In addition they found that digital mammography might be better than film mammography in detecting cancer for women in their 40s with dense breasts, who had not gone through menopause. However, for women aged 40 to 49, the risk of having a false-positive was a little higher with digital mammography compared with film.

An associated report, from the International Prevention Research Institute in Lyon, France, puts the two investigations in context.

Both investigations were funded by The National Cancer Institute, which supports the Breast Cancer Surveillance Consortium. The collection of cancer data was also supported in part by several state public health departments and cancer registries across the United States.

As well as Drs. Kerlikowske and Hubbard, the additional co-authors of both investigations were Diana L. Miglioretti, PhD, of Group Health Research Institute and Bonnie C. Yankaskas, PhD, of the University of North Carolina at Chapel Hill.

In addition to Drs. Hubbard, Kerlikowske, Miglioretti, and Yankaskas, the other co-authors of the study on false positives were Weiwei Zhu, MS, of Group Health Research Institute and Chris I. Flowers, MD, of the Moffitt Cancer Center and Research Institute, in Tampa, FL.

And the other co-authors of the investigation on digital vs. film mammography were Constance D. Lehman, MD, PhD, of the University of Washington, also an affiliate investigator at Group Health Research Institute; Berta M. Geller, EdD, of the University of Vermont in Burlington; Stephen H. Taplin, MD, MPH, of the National Cancer Institute; and Edward A. Sickles, MD, of the University of California, San Francisco.

Written by Grace Rattue

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Does Fertility Treatment Raise Breast Cancer Risk?

Does Fertility Treatment Raise Breast Cancer Risk?

Breast Cancer Diagnosis for Giuliana Rancic Raises Questions About In Vitro Fertilization
By Sonya Collins

When E! News anchor Giuliana Rancic made her breast cancer diagnosis public, there was speculation about whether fertility treatment might have been a factor.
On NBC's Today show, Rancic, 37, said she got a mammogram when her doctor strongly recommended it before starting another round of IVF (in vitro fertilization). On their reality TV show, Rancic and her husband, Bill, have chronicled their previous fertility treatments.
Rancic's diagnosis has raised questions about whether fertility treatment can increase the risk for breast cancer. WebMD got answers from fertility and breast cancer specialists.

Is there a link between IVF and breast cancer risk?

Fertility and cancer experts interviewed for this story agree that there is no strong evidence to connect fertility drugs with increased risk for breast cancer. Oncologists add that there is a need for studies that follow women who have undergone IVF for longer periods of time.

Couldn't the increased levels of estrogen in fertility treatments increase risk for breast cancer?

Exposure to estrogen and progestin after menopause has been linked to increased risk for breast cancer for women in their 50s and 60s, but fertility drugs do not expose women to estrogen at that age, says Samantha Pfeifer, MD. She is chair of the practice committee at the American Society for Reproductive Medicine.
Pfeifer says fertility drugs raise estrogen levels for up to seven days at a time. "Estrogen levels are not significantly raised for a prolonged period of time."

Is it possible that women undergoing fertility treatment have other risk factors unrelated to fertility drugs?

Yes. There are many factors that affect breast cancer risk.
Most women undergoing fertility treatment are over 32 and have never had a child, which is a risk factor for breast cancer, says Jennifer Litton, MD. Litton is a breast medical oncologist at the University of Texas M.D. Anderson Cancer Center.

Are there special recommendations for women who want to undergo IVF but who have increased risk factors for breast cancer, such as the BRCA gene mutation or a family history?

Recommendations about undergoing fertility treatment are no different for women who have breast cancer risk factors. "As long as you don't have a cancer diagnosis," Litton tells WebMD, "at this point, there is no evidence that IVF will increase risk for patients with greater risk factors, even those with the BRCA gene mutation or family history."

Is it common for fertility doctors to recommend a mammogram before a woman undergoes IVF?

Any woman who is trying to get pregnant should be following the regular guidelines for health maintenance. "You want to make sure the Pap smears are up to date and that any routine screening has been done," Pfeifer says. "We follow the established guidelines of mammograms starting at age 40 for women who don't have significant risk factors."
The guidelines about when to start screening mammograms are also controversial.

Is fertility treatment an option for breast cancer survivors?

"It can be an option, but it depends on several factors," says Eric Widra, MD, who chairs the practice committee for the Society for Assisted Reproductive Technologies.
These factors include a woman's age at the time of treatment because fertility naturally decreases over time, and most oncologists recommend a woman be cancer-free for around five years before trying to get pregnant. Future pregnancy also depends on the damage chemotherapy may have done to a women's reproductive system. It is ideal to see a fertility specialist before beginning cancer treatment rather than after.
"What we often do for our patients, especially if they are over 30, is consider fertility preservation before they go through chemo," Litton tells WebMD, "by retrieving eggs and freezing the eggs or embryos. Freezing embryos is the standard. Freezing eggs is still considered experimental."

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Obese Women Have Higher Risk Of Suffering Breast Cancer

University of Granada researchers have proven that overweight women -especially those with morbid obesity- develop this disease at an earlier age.
A total of 524 women with breast cancer participated in the study. The researchers found that women who started menstruating at a very early age between 9 and 10 years- developed breast cancer at a younger age.
Obese women develop breast cancer at a younger age than other women. Furthermore, the likelihood of developing breast cancer is much higher in patients with morbid obesity.
This is one of the main conclusions drawn in an article recently published in the Spanish journal Nutrición Hospitalaria by the University of Granada research group CTS 367, coordinated by the Nursery Department professor María José Aguilar Cordero.
The researchers examined a sample of 524 women diagnosed with breast cancer who were treated at the university hospital San Cecilio from January 2009 to September 2010 in Granada, Spain. They assessed the nutritional status of these patients (normal weight, obesity and morbid obesity) and their age at diagnosis. Women with a family history of breast cancer were separated from those lacking it.
The researchers found that obesity in women is associated with diagnosis of breast cancer at a younger age. This finding contrasts with the results obtained in previous studies that demonstrated that individuals with higher body mass index had lower risk of suffering breast cancer.
Age At First Menstruation
The University of Granada researchers found that women diagnosed with breast cancer at an earlier age were those who started menstruating when younger than 10 years. Thus, age at menarche is determinant in the development and diagnosis of breast cancer, especially in women with morbid obesity.
Therefore, although genetics and family history of cancer are very relevant factors (up to 18% of breast cancer in obese women had a genetic factor), this study proved that obesity -especially the most severe cases- is the most relevant factor in early development of breast cancer.

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Foods That Lower Breast Cancer Risk

The latest on links between breast cancer and diet suggests that consuming an abundance of vegetables, fruits and legumes may help women cut their risks of one type of breast cancer. After 26 years of following more than 86,000 nurses in the U.S., researchers have reported that those whose diets were rich in plant foods, while low on meat, sodium and processed carbohydrates had a 20 percent lower risk of developing estrogen-receptor-negative breast cancer, malignancies that account for about 25 percent of all cases. Here, breast cancer cells lack receptors for estrogen. When estrogen receptors are present, as they are in most cases of breast cancer, treatment can include tamoxifen and other drugs to "block" estrogen's access to cells, thus reducing the risk of recurrence. No drugs are currently available to reduce the risk of recurrence of estrogen receptor negative breast cancer. The dietary findings were published online August 10 by the American Journal of Epidemiology. In other news, a study performed with mice published in the August/September issue of Nutrition and Cancer showed that breast cancer risk dropped significantly when the animals' regular diet included walnuts in an amount that would translate to about 2 ounces a day for humans. Neither of these findings proves that eating vegetables - or walnuts - are directly responsible for the reported risk reductions, but suggest that follow up studies are worth pursuing.
My take? While there's no surefire dietary strategy to prevent breast cancer, we do know that women who gain weight as adults are at higher risk, as are women whose diets include the most meat (compared to women who eat little or no meat). In addition to watching your weight and eating less meat, I also recommend avoiding alcohol (drinking can raise your risk), eating lots of cruciferous vegetables, which give you protective phytonutrients, exercising regularly, which can help lower your risk of many diseases, and avoiding the long term use of estrogen replacement therapy at menopause.

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Poorer Women More Likely to Die From Breast Cancer

 Less-affluent women now face a greater risk of dying from breast cancer than wealthier patients, a new American Cancer Society report finds.

The trend represents a reversal of a previous trend, in which women with greater means had been at a greater risk for dying from the disease.
"In general, progress in reducing breast cancer death rates is being seen across races/ethnicities, socioeconomic status and across the U.S.," said Dr. Otis Brawley, chief medical officer for the American Cancer Society, in a society news release. "However, not all women have benefited equally."
"Poor women," he noted, "are now at greater risk for breast cancer death because of less access to screening and better treatments. This continued disparity is impeding real progress against breast cancer, and will require renewed efforts to ensure that all women have access to high-quality prevention, detection and treatment services."
The report, "Breast Cancer Statistics, 2011" is in the current issue of CA: A Cancer Journal for Clinicians.
More than 230,000 women will face a breast cancer diagnosis this year, and nearly 40,000 will die. The disease is the most common cancer among American women, after skin cancer, according to the report.
However, the overall U.S. breast cancer death rate has been on a steady decline for more than two decades. For women under 50, fatalities fell roughly 3% per year since 1990. For patients over 50, the drop was about 2% per year.
Death rates have gone down in 36 states and the District of Columbia between 1998 and 2007.
Yet the new report finds that death rates have not fallen at the same pace across all racial and socioeconomic lines, with the remaining 14 states experiencing little to no drop-off.
Until the early 1990s, women living in more-affluent areas had a higher death rate than those in poorer neighborhoods. But in the ensuing years, a relatively slow drop in death rates among poorer women has reversed the situation, so that today it is the less- affluent who are burdened with the highest death risk.
Dr. Rachel A. Freedman, a Boston-based medical oncologist with the Dana Farber Cancer Institute, said that less-affluent breast cancer patients face a "perfect storm" when it comes to mortality risk.
"Women from lower economic status have less access to resources, have suboptimal insurance coverage, may receive substandard care and often present with more advanced cancer at diagnosis," she noted. "So it's not surprising that they often face a substandard outcome."
"So it's a really complicated situation ... and that will mean that complicated interventions will be required to tackle this problem," she added. "But unfortunately, I don't see anything happening right now that's going to turn this around in the near term."
-- Alan Mozes

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What Is A Breast Self Exam? Are Breast Self Exams Useful?

While breast self-exams are not recommended as a substitute for breast screening, most experts encourage women to become familiar with the way their breasts look and feel. This familiarity makes it much more likely that any changes might be detected early on. The American Cancer Society says that BSE (breast self-exams) play a small role in detecting breast cancer, when compared to finding a lump by chance or simply being aware of what is normal.

Some women are quite happy to do a BSE after each period. It is a step-by-step approach to examining (observing) and feeling the breasts. Others, however, prefer random checks and general awareness, such as checking while in the shower, getting up in the morning or going to bed at night - a less systematic approach.

It is important that the woman does what feels best for her and does not become over-anxious about whether she has got the technique right.

The aim of a monthly breast self-exam is to report any detected changes to a health care professional immediately.

In some countries, such as Russia and China, studies concluded that BSEs cause such an increase in unnecessary biopsies that they do not recommend BSE, and advise women to attend regular breast screening.

How to do a breast self-exam

• Stand in front of the mirror with your upper body exposed
• Look carefully in the mirror for signs of swelling, redness or dimpling either on the breast, or near it
• Repeat the instruction above in different positions, with hands on hips and arms overhead
• Palpate (touch exploringly) your breasts with the pads of your fingers and seek out any lumps which may be on the surface or deeper inside. Look out for any soreness as you do this.
  
  Move the fingers up and down over the breast.Then start at the nipples and move outwards.
  
  Move the fingers around the nipples in concentric circles moving outwards.
• Some doctors or nurses advise the woman to imagine the breast is divided into four quadrants, and to check each one separately.
• Palpate the area including the part of the breast that extends to the armpit - the axillary tail. You should do this once while standing and once while lying down.
• Squeeze the nipple and check for any discharge. Do not do this if you are breastfeeding.

Pic 1 to 3 involves inspecting the breast with the arms hanging, behind head, and on hips. Pic 4 is the palpitation (touching) of the breast. Pic 5 is palpitation of the nipple. Pic 6 is a BSE while lying down.

Health care professionals say that women who menstruate (pre-menopausal) should perform their BSA at the same point in their cycle each month - hormonal variations during the cycle can cause changes in breast characteristics. Most doctors and nurses advise doing the BSE just after a period, when the breasts are most swollen and tender. Tell your doctor or nurse if you notice any of the following:

• A lump inside the breast or underarm area
• A thickening inside the breast or underarm area
• A hard knot inside the breast or underarm area
• Darkening of the breast
• Swelling anywhere on the breast
• Redness on the breast
• Any alteration in the size of the breast
• Any change in the shape of the breast
• Puckering or dimpling of the skin
• A rash on the nipple
• Scaly skin on the nipple
• Itchiness on the nipple
• Nipple discharge, especially one that starts suddenly. If the discharge is clear (not milky), occurs just on one nipple, has blood in it, or comes out without squeezing, tell your doctor or nurse.
• A pain anywhere that does not go away

In most cases, lumpiness is nothing to worry about - breast tissue has a bumpy texture anyway. If you feel any lumpiness, compare it to the lumpiness in the other breast - most likely it is nothing. If you are concerned, tell your doctor.
Written by Christian Nordqvist

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New Study Explores Immune System Stimulation In Battle Against HER-2/neu Pos...

The Mayo Clinic is excited to announce a Phase I study of a new therapeutic vaccine in HER-2/neu positive breast cancer patients in the fourth quarter of 2011. To understand the importance of this development, the HER-2/neu and the significance of HER-2/neu positive breast cancer must be examined.
Due to a genetic change, cancerous cells produce an excess of HER2 in approximately 1 in 5 breast cancer cases as well as in other forms of cancer. For unknown reasons, HER2-positive breast cancers are less responsive to hormone treatment and tend to be more aggressive than other types of breast cancer.
HER-2/neu is a protein homologous to epidermal growth factor receptor providing growing, dividing and repair signals to cells. Whilst healthy breast cells contain 2 copies of the HER2 gene, some forms of breast cancer develop when a breast cell contains 2 or more copies of the gene which results in over-production of HER2 protein (over-expression) leading to increased growth and division of the affected cells.
HER-2/neu is over-expressed on the cell surface of several cancers, including breast, colorectal, ovarian, and pancreatic carcinomas, supporting the malignancy of several tumors with poor prognosis in cancer patients. With HER-2/neu expressing ~20% to 30% of breast and ovarian cancers it has been identified by the National Cancer Institute as one of the top priorities for the development of cancer drugs.
The common treatment for HER-2/neu positive patients is Herceptin (trastuzumab), a monoclonal antibody that targets HER-2/neu receptors on cells, however, the treatment results in a significant amount of patients (estimated to be ~70%) failing to respond or losing their responsiveness. The authors recommend more widely applicable therapies for this patient population.
So far, previous attempts to develop a vaccine against the Her-2/neu protein proved unsuccessful in overcoming the difficulty of developing a robust and a long-acting immune response by positively stimulating cytotoxic T-cells and T-helper cells in the immune system, which is necessary for a successful vaccine, however, some previous trials managed to progress to clinical trials.
Once stimulated, cytotoxic T-cells identify cancer cells, infiltrate tumors and kill abnormal cells, with T-helper or T-memory cells being responsible for long-term memory, enabling the immune system to continuously recognize abnormal cells.
It has been determined that the function of TAP (Transporters Associated with Antigen Processing - reference 1 provides further background) is significantly reduced in many cancers due to inadequate stimulation of cytotoxic T-cells, resulting in poor recognition of cancer cells. The process can be re-instated by replacing TAP through TapImmune's AdhTAP1 technology, which is similar to turning on a light bulb allowing these cells to 'see' tumor cells.
Dr Keith Knutson and colleagues at the Mayo Clinic, together with collaborators discovered a unique set of peptides (HER-2/neu antigens - reference 2 provides further background) that stimulated these cells in ~ 80% of HER-2/neu positive patients during research on stimulating T-helper cells.
In their clinical evaluation, The Mayo Clinic will be assessing the proficiency of two technologies, the unique peptide antigen and the combination of TapImmune's, TAP vector technology, to stimulate an immune response in HER-2/neu breast cancer patients and to improve patient prognosis and survival rates.
In a concluding statement the authors said,

"We believe that this approach which stimulates two key components of the cellular immune system in HER-2/neu breast cancer patients could have a significant advantage with respect to strength and duration of the immune response. We envisage that the approach will result in an injectable product that will be simple to manufacture,"

..continuing that,

"The initial clinical pathway of cancer vaccines is generally to seek approval for products that can be used as therapeutic vaccines to improve patient survival. However, our ultimate vision on the future use of such vaccines, for the treatment of breast cancer, is to have prophylactic vaccines that can be used at the earliest stage of disease diagnosis, e.g. in situ ductal carcinoma. For those of us who have lost loved ones to breast cancer, who initially presented with this indication, the importance of this goal cannot be overstated."

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