Vitamin D and Breast Cancer: An Overview

Studies of the benefits of vitamin D have been controversial, with some showing significant benefits and other showing none, and most not differentiating between hormone receptor types. The difference often is in the study design. Research on serum vitamin D—the form that circulates in the blood—often find more cancer-fighting evidence. Those that study vitamin D intake are less convincing. This could be because our bodies use vitamin D differently, depending on a variety of factors: age, diet, activity level, and even genetics. Also, serum vitamin D might come from the most natural of all sources—the sun or our diets—whereas vitamin D intake often measures artificial forms. Still, even researchers who study the serum form advocate supplements, especially for people in northern latitudes who do not have the benefit of regular sunny days.

Triple Negative and Vitamin D

A case study of 91 breast cancer patients in Whittier, California found that those with triple-negative were more likely to be deficient in serum vitamin D—doctors measured a form called 25 (OH)D. Fifteen of the patients were triple-negative, and the majority of those—87 percent—had lower levels of the vitamin than other cancer patients, with the remaining 13 percent being borderline low. This ties in with other research on triple negative and on vitamin D, the researchers write: “African American women have the highest breast cancer specific mortality rates, the lowest serum levels of 25(OH)D, and the highest incidence of aggressive triple-negative or basal-like tumors.”

A specific form of active vitamin D3 known as Gemini 0097 substantially reduced the development of both ER- and ER+ breast cancer in rats, according to research done at Rutgers University. Scientists injected rats with breast cancers then treated them with Gemini 0097. The vitamin D slowed the growth of ER-positive by 60 percent and ER-negative by 50 percent. As with all studies in animals, more research needs to be done to determine the effects of Gemini 0097 on human cancers. One benefit so far is that Gemini 0097 is less toxic than other forms of synthetic vitamin D and does not lead to an overload of calcium, the vitamin’s most common side-effect.

Research Reviews on Vitamin D and Breast Cancer

Several research reviews support the benefits of vitamin D. According to a 2009 review done by scientists at the University of California, San Diego, low levels of serum Vitamin D are connected to a variety of cancers, including breast, colon, ovarian, renal, pancreatic, and aggressive forms of prostate, and other cancers. Researchers projected that raising our intake of vitamin D would prevent 58,000 new cases of breast cancer each year; 2,000 mg a day, they say, can increase serum levels to a healthier range without other risks.

In a 2006 review, scientists cited numerous studies that link both calcium and vitamin D to breast cancer risk for premenopausal and well as postmenopausal women. And in a third review, in 2007, researchers noted that 2000 IU a day of Vitamin D3 can reduce the risk of breast cancer by 50 percent.

Research on 16,818 participants in the Third National Health and Nutrition Examination Survey (NHANES III) determined that women with higher levels of serum vitamin D (over 25 ng/mL) had only about one fourth the mortality rate from breast cancer as those with lower amounts. Survey participants were 17 years or older at enrollment and were followed from 1988–1994 through 2000.

Research on Vitamin D Supplements and Breast Cancer

Yet a long-term study—seven years—of postmenopausal women as part of the Women’s Health Initiative found no relationship between Vitamin D and breast cancer. Researchers gave women 1000 mg of elemental calcium with 400 IU of vitamin D3 daily. Those women had no lower risk of breast cancer than those receiving a placebo.

And research using data from the Cancer Prevention Study-II Nutrition Study also found no association between postmenopausal breast cancer risk and levels of Vitamin D, regardless of hormone receptor status, body mass index, postmenopausal hormone therapy, weight gain, season of the year, or calcium intake. However, researchers did note that:

• the source of Vitamin D might be important, with women who get the vitamin through their diet—in fortified milk or fish, for example—having higher levels circulating in their bodies. Also, dietary Vitamin D is strongly correlated with calcium, which may be effective in fighting breast cancer.

• Women living at northern latitudes—above 37° —get less Vitamin D from the sun and were more likely to have breast cancer than those in southern latitudes.

What the research says on breast self-exams

The recommendations by the U.S. Preventive Services Task Force to forego breast self-exams (BSE) was based on research on the effectiveness of the exams. I found three studies, but the newest was in 2003. I continue to search for newer studies.

The studies below show no benefit, but have some flaws. In the Russian study, women did not follow through with the exams, so testing the BSEs effectiveness was compromised. And the Chinese study showed an equal number of cancers in the group that learned self-exams and the group that didn’t. This doesn’t address the issue of whether some of the cancers in the group that learned BSEs were found early enough to be treated.

The studies:

In a clinical tiral in St. Petersburg, Russia, 122,471 women between 40 and 64 were trained to perform BSE. One problem: many of these women did not actually practice self exams after they were taught how; after 5 years, only 55.8 percent of the women practiced BSE at least 5 times per year. After 9 years, the group that was taught self exams and the group that was not taught them had the same mortality rate from breast cancer, with no difference in the stage of breast cancers diagnosed. Self-exams did lead to a higher rate of biopsies for benign lumps. This was published in the journal Vopr Onkol in 1999.

In a randomized trial in Shanghai, China, 267,040 women ages 31-64 were taught BSE and were regularly reminded to practice the technique. Most women followed through during the study period and learned the BSE well. After about 10 years, the group that was taught self-exams and the group that was not taught them had the same breast cancer mortality rate, also with little evidence that BSEs led women to find their cancers earlier. The group that learned self-exams and the group that didn’t found the same number of cancers each year of the study. In addition, the number of cancers that had spread to the lymph nodes was similar in each group. Again, self-exams had more benign lumps than the control group did. This was published in the Journal of the National Cancer Institute in 2002.

A third study the Russian and the Chinese trials together and, likewise, found no benefits to breast self-exams. The review found twice as many biopsies with benign results in the groups taught self-exams compared to the groups who were not taught self-exams. This was published by the Cochrane Collaboration in 2003.

Sources:

Semiglazov VF, Moiseenko VM, Manikhas AG, et al. [Interim results of a prospective randomized study of self-examination for early detection of breast cancer (Russia/St.Petersburg/WHO)]. Vopr Onkol 1999;45:265-71.


Thomas DB, Gao DL, Ray RM, et al. Randomized trial of breast self-examination in Shanghai: Final Results. J Natl Cancer Inst 2002;94(19):1445-57.

Kosters JP and Gotszsche PC. Regular self-examination or clinical examination for early detection of breast cancer (Review). John Wiley & Sons Ltd. (for The Cochrane Collaboration) 2008.

What do the New Mammography Guidelines Really Say?

You’ve read about them and heard about them and talked about them to your office colleagues. But what are the new standards presented b the U.S. Preventive Services Task Force ( USPSTF)?

The guidelines are published in the Annals of Internal Medicine and you can read the entire manuscript there.

Some highlights of the paper. The recommendations are simple. They are:

The USPSTF recommends biennial screening mammography for women between the ages of 50 and 74 years.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of clinical breast examination beyond screening mammography in women 40 years or older.

The USPSTF recommends against clinicians teaching women how to perform breast self-examination.

The USPSTF concludes that the current evidence is insufficient to assess additional benefits and harms of either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer.

Task force members maintain that research supports mammogram screening for women over 50, but not for women 40-49:

There is convincing evidence that screening with film mammography reduces breast cancer mortality, with a greater absolute reduction for women aged 50 to 74 years than for women aged 40 to 49 years. The strongest evidence for the greatest benefit is among women aged 60 to 69 years.

Notice that they mention film mammography. That is an outdated method. Digital mammograms are offered at most—if not all—breast cancer centers. They are more precise and more effective in finding cancers in younger women. In reference to digital mammos, task force members say, in research-ese, that evidence is lacking.

As for breast self exams, the write:

Adequate evidence suggests that teaching BSE does not reduce breast cancer mortality.

I am looking for research on self-exams. My question: Are they studied all that much? If no absolute evidence exists, is that because the subject has not been adequately studied? I will post what I find.

The task force also worried about the harm caused by mammograms and self-exams, although they say these harms are small or moderate.

All in all, not that convincing a case, and a seriously confusing presentation. Shame on them for taking women’s health concerns so lightly that they didn’t think this through better.

Who Is Behind the New Breast Cancer Guidelines?

Information on the panel that recommended this week that women stop doing breast self-exams and start mammograms every other year at age 50, Currently, the National Cancer Institute and the American Cancer Society recommend yearly mammograms after age 40 and both are standing by those guidelines.

The U.S. Preventive Services Task Force, the panel that created the new guidelines, is part of the U.S. Department of Health and Human Services. That agency comes under the direction of Secretary of Health and Human Services, Kathleen Sebelius, who opposes the recommendations, supporting existing standards.

It seems we have a bit of a failure of communication here. Did the panel just make its recommendations without checking with the brass first? Or did they run the new standards by Sebelius's staff, which did not see the army of red flags attached to such a controversial, confusing proposal?

Whatever the case, the NCI, ACS, and the Secretary of Health and Human Services all oppose the new guidelines.

Meanwhile, who are the members of the task force that came up with this brilliant plan? The panel consists of 16 medical professionals:

•Seven men, including the chair, Bruce N. Calonge, MD, MPH, Chief Medical Officer and State Epidemiologist
Colorado Department of Public Health and Environment.

•Nine women, including vice chair Dianne Petittie, MD, MPH, Professor of Biomedical Informatics
Fulton School of Engineering
Arizona State University. (see NOTE below)

•13 MDs

• 4 Ph.Ds, 2 of whom have backgrounds in nursing

• 8 are administrators of some type

• 13 are academics

• 1 is primarily a practicing professional

• Not one member is a breast cancer surgeon.

It looks like we have quite a few members who are removed from actual patients, members for whom research may have no human face. There were no breast surgeons and there were only two nurses, although they were no longer working in nursing. (As any breast cancer survivor knows, nurses are the real forces behind treatment.) The women did outnumber the men, but only barely. And, of course, what is really lacking on the panel, as is the case on most medical boards, are patients. Breast cancer survivors. People who understand what this all actually means to women's lives, who know that women are already frightened about breast cancer and don't need more confusing guidelines and a seemingly heartless understanding of the benefits of mammograms and self exams.

NOTE: Did you wonder, as I did, what Biomedical Informatics is all about? Here's an explanation from the Arizona State University's website:

Biomedical informatics, check here. is an emergent field, grounded in the principles of computer and information sciences, telecommunications, mathematics and statistics, cognitive and social sciences, biological signal processing, clinical and basic biological and medical science, decision science, epidemiology and biostatistics, and public health. In accordance with the definition by the American College of Medical Informatics and supported by the National Institutes of Health, the taskforce uses the term “biomedical informatics” to describe the union of computing and informatics with basic biological and medical research, clinical practice, imaging, and public health.

New Mammography Guidelines: What Do They Mean to Women with TNBC?

What's the message to women with triple-negative breast cancers in the current brouhaha over changes in mammography and self-exams from the US Preventive Services Task Force?

The recommendation that women begin mammograms every other year after age 50, rather than yearly after age 40, is terse and to-the-point, with one qualifier:

The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient's values regarding specific benefits and harms.

If we take that broad statement and narrow it, "patient context" would include issues such as the BRCA1 or BRCA2 gene and a family or personal history of breast cancer.

We know that the BRCA mutation is linked to triple negative, so women who have that in their family will still be encouraged—I hope—to have a mammogram as soon as they are found to carry the BRCA gene. And those with a family history will still—I hope—have yearly mammograms beginning ten years before the age at with their closest family member was diagnosed.

The fact is that triple negative affects women who are not covered by current guidelines--it disproportionately affects women under 40. And, while there is the BRCA link, women can be the first in their family to discover they have the gene and they can have triple negative without the gene—so they would not have been vigilant about mammograms. And, mammograms have been less effective in finding IBC—inflammatory breast cancer—which is linked to triple negative in some women.

Also, as I have noted in previous blogs, MRIs may be more effective for high risk women, but in conjunction with mammograms.

So mammography is already an imperfect tool for triple-negative.

I suspect that the guidelines will hit some bumps before—and if—they are adopted. Breastcancer.org strongly disagrees with the changes, noting, among other things, that they are based on older types of mammograms (film rather than digital) and false assumptions on what course to take after diagnosis. They also, I think, make an important, and poignant point about the "limited" success of mammograms:

Expressed as nameless, faceless numbers, the 3% decrease in breast cancer survival might seem like an acceptable trade-off when compared to the economic benefits of changing breast cancer screening policies. But breast cancer affects a very large number of women, so 3% of that number is not insignificant. The reality is that more women -- mothers, daughters, sisters, grandmothers, and aunts -- will die each year from breast cancer, which is neither reasonable nor acceptable.

The guidelines also recommend against teaching breast self exams. According to Dr. Susan Love, the effectiveness of these has never been supported by research. Women can find benign cysts and worry over them and get tested unnecessarily.

But mammograms can also find breast cancer!

This is far from scientific, but I discovered my lump in the shower and my gynecologist also felt it and a mammogram discovered it. Yes, this is a universe of one, but the cancer was aggressive, so I was blessed that it was found early.

So, what are we supposed to do? Talk to your doctor and let your concerns be known. Be vocal and speak out through whatever forum you can find—letters to your senators and representatives and to your local paper. Connect with advocacy groups.
Most important, take care of your own health. Be aware of changes in your breasts—not just lumps, but any hardening, or variations in shape or feel. And, if you notice changes, be vigilant about getting tested. The fact is, under current guidelines, this was already a problem. So the reality remains that we are the ones most vested in our own health, and it is up to us to continue the good fight to get the care we need.

And, if you are at high risk, continue to get mammograms, but advocate for coupling them with MRIs. As I read it, the recommendations do not change that. If anything, I see the recommendations saying that highly aggressive cancers such as triple negative should get more—not less—attention.

It's always something.

Changes in Mammography Screening: Dr. Susan Love's Take

In a blog post yesterday, Dr. Susan Love noted that the current American standards for mammography are at odds with European models, yet are no more successful in saving lives. The new guidelines for mammography from the U.S. Preventive Services Task Force suggests that women now get mammograms after age 50, rather than the current 40, and have them every other year, rather than yearly as is the current recommendation. Research, she says, supports this decision.

Mammograms, she says, find cancers that might even go away on their own, but are less successful at finding the more aggressive forms, which certainly would include triple negative:

We now know that there are at least five different kinds of breast cancer based on their molecular biology. Some breast tumors are so slow growing and are so unlikely to spread that they will never do any harm. Others grow and spread very quickly. The idea that they all can be “caught early” is wishful thinking. In fact screening is best at finding the “good ones” that might even disappear if left alone.

We should be to be vigilant, she says, in finding the cancer that need immediate treatment and are deadly rather than focusing so much attention on slow-growing, less threatening forms.

The goal of breast cancer screening should be this: to find the cancers that have the potential to kill you, so that an intervention is necessary and can make a difference. We need to stop finding the cancers that will never do anything, and stop over-treating women who have them.

Read her entire blog here.

Breastcancer.org Opposes Changes in Mammogram Guidelines

The Annals of Internal Medicine today published the US Preventive Services Task Force recommendation on breast cancer screening that recommends mammography screening start at age 50, and then be done every other year after that, except for women at high risk. The current breast cancer screening guidelines call for annual screening mammograms start at age 40 - and be done annually. Breastcancer.org strongly disagrees with this proposal.

From a news release from Breastcancer.com:

PHILADELPHIA, November 16/PR Newswire-USNewswire/-- "The recommendation to change breast screening is a huge step backwards," says Dr. Marisa Weiss, a leading breast oncologist and founder and president of Breastcancer.org.

The proposed new guidelines call for mammograms to start at age 50 and to be done every other year instead of every year starting at age 40, as recommended by current guidelines.

"The data simply does not account for the human perspective. It would be an enormous mistake to allow outdated data using older technology provided by computer-generated analysis to dictate how health care professionals screen women for early detection of breast cancer. These are real people with their lives at stake... for whom mammography has a proven survival benefit."

The letter to the Breastcancer.org community follows:

Dear Breastcancer.org Member:

The U.S. Preventive Services Task Force recently recommended dramatic changes to current breast cancer screening guidelines. Breastcancer.org is strongly opposed to these recommendations.

The proposed new guidelines recommend starting regular screening mammograms at age 50, rather than at age 40 as current guidelines recommend. They recommend screening before age 50 only for women with a much-higher-than-average risk of breast cancer. The proposed new guidelines also call for mammograms to be done every other year instead of every year, as recommended by current guidelines.

At Breastcancer.org, we are deeply troubled by both the analysis that led to these proposed guideline changes and the effect these proposed changes would have on the health and lives of women. Our specific concerns:

• The analysis was based on older mammography techniques, meaning the researchers mostly looked at results from film mammograms instead of digital mammograms.
• The analysis was based on some inaccurate assumptions about optimal treatment after breast cancer is diagnosed. For example, it assumed that women diagnosed with hormone-receptor-positive, early-stage breast cancer would receive and benefit from hormonal therapy but not chemotherapy, even though we know that many of these women do receive and benefit from chemotherapy after surgery. Inaccurate assumptions like this may have caused the researchers to underestimate the number of lives that would be lost should the proposed changes in screening be adopted.
• The analysis did not adequately consider the combined benefit of early detection (with current screening guidelines) and new treatments that have resulted in steadily improving survival rates in recent years. Screening cannot be looked at in isolation as a snapshot. Screening happens as we continue to improve both diagnosis and treatment. But we can’t treat what isn’t diagnosed.
• The proposed guideline changes would mean that many breast cancers would be diagnosed at a later stage, making it harder to become cancer-free. Later-stage diagnoses result in more women with metastatic disease (that has spread to other parts of the body) and more women with large or multiple cancers requiring mastectomy (too late for breast-conserving treatments).
• The proposed guideline changes would mean that younger women would be diagnosed later. Breast cancer in younger women tends to be more aggressive, so early diagnosis and treatment is more critical for them. It is the lives and futures of younger women that would be lost if the proposed changes are adopted.

Expressed as nameless, faceless numbers, the 3% decrease in breast cancer survival might seem like an acceptable trade-off when compared to the economic benefits of changing breast cancer screening policies. But breast cancer affects a very large number of women, so 3% of that number is not insignificant. The reality is that more women -- mothers, daughters, sisters, grandmothers, and aunts -- will die each year from breast cancer, which is neither reasonable nor acceptable.

We at Breastcancer.org encourage medical professionals and everyone affected in any way by breast cancer to raise their voices against these surprising and dramatic proposed changes in the guidelines for breast cancer screening. Our belief is that lives should be saved, not lost, and our commitment to you is that we will continue to strongly advocate for policies that support this fundamental mission.

Marisa C. Weiss, M.D.
President and Founder, Breastcancer.org
Director of Breast Radiation Oncology, Director of Breast Health Outreach
Lankenau Hospital

Maxine Jochelson, M.D.
Director of Radiology
Evelyn H. Lauder Breast Center
Memorial Sloan-Kettering Cancer Center
Professional Advisory Board, Breastcancer.org

Emily F. Conant, M.D.
Professor of Radiology, Chief of Breast Imaging
Hospital of the University of Pennsylvania
Professional Advisory Board, Breastcancer.org

Are MRIs Better at Screening for Women at High Risk of Breast Cancer?

Mammograms are the test of choice for most breast cancer screening, and studies have shown that they save lives.  But for high-risk women—those with dense tissue, a family history of breast cancer, the BRCA1 or BRCA2 gene, or previous breast cancer—the MRI might be a better choice.

The difference between the two:

Mammography is based on a single two-dimensional projection of the breast.  MRIs offer a three-dimensional image.  And while, on the face of it, MRIs sound automatically superior, they also can offer the risk of false positives—suggesting cancer where there is none.  That is why mammograms are still recommended for women at low or moderate risk.  

Several studies have looked at the difference between the two for high-risk women:

Research published  in the American Journal of Roentgenology (April, 2009)  demonstrated that a specific type of MRI—the newest generation 3T MRI—offered early diagnosis of breast cancer for women in hish risk categories.  Researchers at the University of Toledo studied 434 high risk women between May 2006 and May 2007.  The 3T MRI detected all of the 66 malignant tumors—a 100 percent rate of effectiveness—while mammograms were 86.4 percent accurate and sonogams 81.8 percent accurate.   This rate of accuracy was superior to the older generation of MRIs—the 1T and 1.5T models.  In their conclusions, researchers recommended MRIs only for high-risk women, however, as mammography is effective, and far less expensive, for women at normal or low risk. 

Research in the journal European Radiology (May, 2008) determined that MRIs may detect tumors associated with the BRCA gene better than mammography.  These tumors often look like benign lesions, with a rounded shape or sharp margins, and MRIs may be better at differentiating between benign and malignant tumors. 

Researchers in England studied the effectiveness of MRIs versus mammograms as part of the ongoing MARIBS (magnetic resonance imaging in breast cancer study). The research, published in Breast Cancer Research (November, 2009)  included 837 women with no symptoms, but with the BRCA1 or BRCA2 gene or first-degree relatives with breast or ovarian cancer.  Fifty-six of the women ultimately developed breast cancer.  Of those, 19 were diagnosed during the study and 37 were diagnosed later. They found that MRIs were more effective in identifying cancer in women carrying the BRCA1 mutation and, overall, provided a clearer definition of potentially cancerous tissues.  They stopped short of recommending MRIs for general screening, though, because the number of women with cancer in their study was so small that their findings could be due to chance.

Based on these and other studies, the American Cancer Society has revised it screening guidelines and now recommends MRIs in addition to yearly mammograms for women who meet at least one of the following conditions:        

•they have a BRCA1 or BRCA2 mutation

•they have a first-degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation, even if they have yet to be tested themselves

•their lifetime risk of breast cancer has been scored at 20%-25% or greater, based on one of several accepted risk assessment tools that look at family history and other factors

•they had radiation to the chest between the ages of 10 and 30

they have Li-Fraumeni syndrome Li-Fraumeni syndrome, Cowden syndrome,  or Bannayan-Riley-Ruvalcaba syndrome, Bannayan-Riley-Ruvalcaba syndrome or may have one of these syndromes based on a history in a first-degree relative.

 

 

Disease-free Survival Higher Than 90 Percent for Early-Stage Cancers

SURVIVAL RATES FOR TRIPLE NEGATIVE BREAST CANCER

Research published online November 2 in the Journal of Clinical Oncology  provides additional data on survival rates of women with TNBC or other forms of hormone-negative with early-stage disease—small tumors that have not spread to the lymph nodes.

The research focused on Her2-positive disease (I recently posted about another recent study on Her2-Positive), but I found the information on survival rates for TNBC and other forms of hormone-negative to be encouraging.

The researchers found the following for women with tumors smaller than 1 centimeter that had not spread to the lymph nodes:

• 92 percent five-year disease-free survival rate for patients with triple-negative breast cancer (ER-negative, PR-negative, and Her2-negative).

• 91 percent  five-year disease-free survival rate for patients with hormone-receptor negative (ER-negative or PR-Negative), but Her2 positive.

• 99 percent  five-year disease-free survival rate  for patients with hormone-receptor positive and Her2-negative. WHoaaaaa!!!!

• 92 percent  five-year disease-free survival rate  for patients with hormone-receptor positive and Her-2 positive.

The research was conducted by doctors at the Istituto Europeo di Oncologia in Milan. Researchers reviewed 2,130 women who had been treated between 1999 and 2006 for early-stage cancer. Of these, seven percent (150) were Her2-positive.

All in all, great stats, no matter what, but significantly different from the stats on research at the M.D. Anderson Clinic that showed an 86.4 percent five-year disease-free survival for women with Her2-negative. Likewise, as I blogged recently, studies in China showed a 73. 8 percent 5-year disease free survival rate for triple-negative, way below the 92 percent here.

Why the difference? This study was done on Italian women; the M.D. Anderson studied women treated in the United States and the Chinese study looked at, of course, Chinese women, so there are no doubt other important variables, like diet, exercise, or genetics. Again, this is not one disease--each woman is different.

In the recent Her2 studies, however, Her2-positive status did affect survival rates, regardless of hormone-receptor status. Women with Her2-positive can improve their odds with Herceptin (trastuzumab) and researchers in both studies say the drug should be considered even for women with early-stage disease.

If you must get breast cancer, your best bet is ER+, PR+ and Her2-. A better bet, of course, is to avoid it.

Source: Curigliano, Giuseppe, Viale, Giuseppe, Bagnardi, Vincenzo, Fumagalli, Luca, Locatelli, Marzia, Rotmensz, Nicole, Ghisini, Raffaella, Colleoni, Marco, Munzone, Elisabetta, Veronesi, Paolo, Zurrida, Stefano, Nole, Franco, Goldhirsch, Aron. “Clinical Relevance of HER2 Overexpression/Amplification in Patients With Small Tumor Size and Node-Negative Breast Cancer.” Journal of Clinical Oncology. Early Release, published online ahead of print Nov 2, 2009.

Early-Stage Her2 Positive Tumors Can Be High Risk

Even early-stage tumors—one centimeter or smaller—can carry a high risk of recurrence if they are Her2, say researchers at the M.D. Anderson Cancer Center. In research published online in the Journal of Clinical Oncology, scientists found that women with Her2-positive breast cancer face a risk of recurrence 2.68 times higher than those with Her2-negative cancers. Some stats:

• The study included 965 patients treated between 1990 and 2002.

• The median age at diagnosis was 57 years.

• More than 10 percent—98 patients—were Her2 positive.

• 77 percent were hormone-receptor-positive.

• 13 percent were triple negative.

• Those with Her2-positive tumors faced a five-year recurrence-free survival of 77.1 percent; patients with Her2- negative tumors had a five-year recurrence-free survival of 86.4 percent.

What does this mean to women with triple negative breast cancer—ER-negative, PR-negative, and Her2-negative—or those with other combinations of ER and PR status? That was not the focus of the study, but this research does demonstrate the complexity of breast cancer as a whole. In previous research, scientists have determined that triple negative cancer is primarily basal in nature, making it a separate and very specific disease. And new categories of breast cancer include luminal A and B, basal-like, and Her2-positive—triple negative is not included as a specific subtype.

Some women with triple negative do not have the highly aggressive basal-like tumors. And, for some, perhaps being Her2-negative might actually be a positive. Again, our cancers are not one-size-fits-all. And, while we need more research, we are making progress.

Breast Cancer Changes Receptor Status As It Spreads

Breast cancer that has spread to the lymph nodes may change receptor status in the process—from estrogen-negative, for example, to estrogen-positive. One-third of the 211 tumors studies changed form, according to research published in the Annals of Oncology.

Researchers at the Breakthrough Breast Cancer Research Unit at the University of Edinburgh found that 82 of the tumors that had spread from the breast to the lymph nodes changed receptor status. Of these, 20 changed from estrogen negative to estrogen positive.

The implications of this are significant—some women with an original TNBC diagnosis, for example, might end up benefitting from tamoxifen or Arimidex. Researchers suggested additional tests be done on tumors that have spread to the lymph nodes.

Recent Studies of TNBC: Most Women Survive

SURVIVAL RATES FOR TRIPLE NEGATIVE BREAST CANCER:

Two recent studies in China add definition to the characteristics of triple negative breast cancer in an Asian population:

In research published in Clinical Oncology August 25, 2009 on 770 breast cancer patients at Shenzhen People’s Hospital, 17.1 percent, or 130 cases, were triple negative. The characteristics of TNBC patients:

• 68.9 percent, or 91 patients, were premenopausal

• 53.8 percent, or 71 patients, had tumors larger than 2cm

• 39.4 percent, or 52 patients, had lymph node metastasis

• At a median time of follow-up of 63 months, 33 patients (25 percent) relapsed and 20 died. Twenty-three patients had at least two organs metastasis.

• The 5-year disease-free survival rate was 73.8 percent and the 5-year overall survival rate was 85.7 percent.

And in a study published online in advance of publication in Modern Pathology October 23, 2009 on 7048 breast cancer patients at the Department of Pathology, Singapore General Hospital, 11 percent were triple negative. Eighty-four percent of these were basal-like.

The major take-away here, to me, is that 73.8 percent of the triple negative breast cancer cases survived five years disease-free. Overall, 85.7 percent survived overall. This is great news to those newly diagnosed women who are terrified. The great majority of TNBC women survive.