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

Not all women with hormone-negative breast cancer are triple negative. Some odd balls, like me, have a mix of positives and negatives—I am weakly positive for progesterone. Research published online November 2 in the Journal of Clinical Oncology sheds additional light on these differences and 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 five-year disease-free survival rates for women with tumors smaller than 1 centimeter that had not spread to the lymph nodes:

• 92 percent for patients with triple-negative breast cancer (ER-negative, PR-negative, and Her2-negative).

• 91 percent for patients with hormone-receptor negative (ER-negative or PR-Negative), but Her2 positive.

• 99 percent for patients with hormone-receptor positive and Her2-negative. WHoaaaaa!!!!

• 92 percent 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

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.

PARP Inhibitor Clinical Trial Seeks Women with TNBC in Michigan

From a University of Michigan news release:

October 28, 2009 -- A clinical trial for women with an aggressive form of metastatic breast cancer is now open at Beaumont Hospital, Royal Oak, and will open soon at the University of Michigan Comprehensive Cancer Center in Ann Arbor, the only sites in the state to be designated as study locations. The trial features a novel drug that is seen as a significant breakthrough in the treatment of triple negative breast cancer or TNBC.

The hospitals are seeking a limited number of women with TNBC to test an experimental medication, BSI 201, which is a poly (ADP-ribose) polymerase or PARP inhibitor. PARP is an enzyme that normal cells use to repair DNA when it is damaged. It is thought that cancer cells also use PARP to overcome the effects of chemotherapy, allowing the cells to repair damage from chemotherapy and therefore continue to grow. When used in conjunction with traditional chemotherapeutic drugs that damage the DNA of the cancer cell, this targeted PARP inhibitor selectively blocks a cancer cell's ability to repair itself, thus causing the cancer cell to die. MORE.

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UC-Berkeley Gets Research Grant for TNBC

UC Berkeley is establishing a research center to focus on triple negative breast cancer. The center is a collaboration between researchers at UC Berkeley, Lawrence Berkeley National Laboratory, UCSF and San Francisco's Helen Diller Family Comprehensive Cancer Center. It is supported by a $15.7 million grant over five years from the National Cancer Institute.

Cisplatin is the most active of chemo drugs tested for TNBC

Lab tests using cisplatin, doxorubicin, cyclophosphamide (4HC), and docetaxel against breast tumors showed that cisplatin was most effective against triple negative cancers. In research presented at the 2009 Breast Cancer Symposium of the American Society of Clinical Oncologists:

• ER- breast cancer is more sensitive to cisplatin than ER+ breast cancer.

• Her2- is slightly more sensitive than Her2+

• ER- /Her2- breast cancer is more sensitive than ER-/Her2+.

So, if you add up the negatives, that means that triple negative gets a special boost from cisplatin.

Researchers also noted that breast tumors defined as “poorly-differentiated” are more sensitive to cisplatin than moderate and well- differentiated tumors

The researchers’ conclusion: “Cisplatin is the most active of the four tested drugs in TNBC.”

Lip Gloss Helps TNBC research

Perk up your lips and help with breast cancer research--20 percent of the sales Sealed With a Cure lip gloss will go to triple negative research. A product of the Triple Negative Foundation and Purple Lab Cosmetics, the gloss is made of healthy ingredients like mangosteen and echinacea, and is paraben-free.

Vanderbilt Gets $4.7 Million for Triple-Negative Research

From Vanderbilt Medical Center's Weekly Newspaper:

Researchers at Vanderbilt University Medical Center have received a two-year, $4.7 million “Grand Opportunities” stimulus grant from the National Institutes of Health to launch a ground-breaking cancer drug discovery program.

The Vanderbilt Molecular Target Discovery and Development Center, a joint effort of the Vanderbilt Institute of Chemical Biology (VICB) and the Vanderbilt-Ingram Cancer Center, initially will hone in on “triple-negative” breast cancer, a particularly deadly form of the disease.

Researchers will try to identify genes that are the “drivers” for the different subtypes of triple-negative breast cancer, and then fashion drugs to block the action of the proteins encoded by the genes, with the intent of killing the cancer cells.

“The beauty of this approach is that if you end up with drugs at the end of this whole process, you already know which patients should get them,” said VICB director Lawrence Marnett, Ph.D., and the grant's principal investigator. More.

More on Vitamin D: Does it Help Prevent Breast Cancer?

Studies have been inconsistent in finding a relationship between Vitamin D and breast cancer. Now, recent research continues this ambiguity. A study published in the journal Breast Cancer Research in August 2009 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. This, however, could be due to chance, researchers say.

Of three previously published studies, two found a relationship between Vitamin D and breast cancer:

• An analysis of 701 cases from the Nurses' Health Study found a 27 percent lower relative risk of breast cancer in women with higher levels of Vitamin D.

• An analysis from the National Health and Nutrition Examination Survey (NHANES) reported a relative risk for fatal breast cancer among women with low levels of Vitamin D.

• Among 1005 postmenopausal cases in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, no association was found between Vitamin D and breast cancer risk.

So, what do we make of this? My conclusion: There is no risk found in taking Vitamin D, so let's make it part of our diet. If there is a chance it helps, why not take it? Dietary sources are better than supplements. The National Institute of Health provides an overview of Vitamin D and provides a list of its sources. The best source: cod liver oil. Sure, it tastes icky, but breast cancer is no picnic either.

NOTE, this study used the terminology serum 25-hydroxyvitamin D (25(OH)D or, simplified, 25(OH)D. For clarification of this terminology, check out the Medline Plus Encyclopedia. Basically, the terms refer to the blood test that measures levels of Vitamin D in the blood. The normal range is 30 to 74 nanograms per milliliter.

Race Not a Factor in Pathologically Complete Response

According to researchers at the M.D. Anderson Cancer Center, pathologically complete response (PCR) is a primary factor for cancer survival, regardless of race.

The study consisted of 2,074 patients diagnosed with Stages II and III breast cancer who were treated at the M.D. Anderson between 1994 and 2008. Of these:

• 1,334 (64.3 percent) were white, with a 12.3 percent PCR.

• 302 (14.6 percent) black, with a 12.5 percent PCR.

• 316 (15.2 percent) Hispanic, with a 14.23 percent PCR.

• 122 (5.9 percent) "other" race groups, with a 11.5 percent PCR.

The median age was 50. All received neoadjuvant—before surgery—anthracycline- and taxane-based chemotherapy.

At a follow-up of 30 months, there were 438 recurrences and 327 deaths. The recurrence-free survival (RFS) and overall survival (OS) rates were:

• 71percent and 79 percent in whites.

• 60 percent and 57 percent in blacks

• 76 percent and 79 percent in Hispanics

• 75 percent and 84 percent in "other.”

"Our findings confirm pathological complete response is a strong prognostic indicator and a surrogate for good survival, despite a patient's race, and that it's vital we continue to strive towards achieving this milestone for all women with breast cancer," said Mariana Chavez MacGregor, M.D., a medical oncology fellow at M. D. Anderson. "The study also mandates that we continue to research the differences across races in breast cancer."

Read the complete news release here.

Support Breast Cancer Research and Win Great Stuff

Looking for a special way to celebrate your disease-free survival? Or a plain old birthday or anniversary? How about five days at an eco-lodge in Ecuador for two? Or a Namibia Safari trip? Bid on anything from a survivor necklace to a handbag, a Nextar GPS, or a set a soy candles in the breastcancer.org online auction. Support breast cancer research and get the chance to win great goodies. Bidding closes October 25 at 8 p.m.

Drug Significantly Reduces Triple Negative Brain Metastases in Mice

The drug Vorinostat prevented the formation of brain metastases of triple negative breast cancer in mice by 62 percent, according to research in the September 29 journal Clinical Cancer Research. The drug crosses the blood-brain barrier, which in the past has been a literal wall to drugs entering the brain, making brain cancer largely untreatable. According to the study’s researchers, from the Center for Cancer Research at the National Cancer Institute, Vorinostat works on both strands of the cancer DNA, slowing the rate of tumor growth. They suggest that it might be an effective cancer fighter in combination with other drugs or radiation.

Source: Palmieri D, Lockman PR, et al. Vorinostat Inhibits Brain Metastatic Colonization in a Model of Triple-Negative Breast Cancer and Induces DNA Double-Strand Breaks. Clin Cancer Res. Sept. 29, 2009. Vol.15, No. 19.

Register for Des Moines' Race for the Cure

Des Moines' Susan G. Komen Race for the Cure:

October 24, 2009, Iowa Capitol Grounds.

Register here.

Federal Stimulus Money Goes to Triple Negative Research

University of Chicago researchers have been awarded $800,000 from federal stimulus funds for a clinical study on treatment of triple-negative breast cancer. The award is part of $5 million in nationwide grants.

Diabetes Drug Could Be Effective in Fighting Triple Negative

The diabetes drug metformin, used in conjunction with the chemo drug doxorubicin, effectively eliminated cancer stem cells in laboratory tests at the Harvard Medical School, according to research published online September 14 in the journal Cancer Research. Cancer stem cells are thought to initiate tumors; they are resistant to standard cancer treatment.

Researchers studied four genetically different cancer types, including triple negative, and determined that the drug combination eliminated existing tumors and prevented regrowth; neither drug alone was effective against the cancer cells.

As a result of this tests, clinical trials are being planned on the use of metformin and doxorubicin in women with early stage breast cancer. Enrollment of patients may begin next year.

Source: Hirsch, Heather A., Iliopoulos, Dimitrios, Tsichlis, Philip N., Struhl, Kevin
Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission
Cancer Res 2009 0: 0008-5472.CAN-09-2994

PARP Inhibitors: A Personal Story about TNBC

Sharon Price tells her story of how PARP inhibitors and chemo have helped her survive triple-negative breast cancer that spread to her lungs. Watch it here, on WAVY-TV in Norfolk, VA.

Is there a link between triple negative and inflammatory breast cancers?

A reader recently asked me about the connection between IBC and triple negative breast cancer (estrogen-receptor-negative, progesterone-receptor negative, and Her2-negative). The results are mixed.

According to the Inflammatory Breast Cancer Research Foundation, most cases of IBC are also triple negative, although I could find no citations to support that claim.

In recent research through the American Society of Clinical Oncology on women with TNBC, 12 percent of the women with TNBC also had IBC.

But, in a study in the journal The Breast 52 percent of the women with IBC were Her2 positive, which means they cannot be triple negative, as Her2-negative is the third part of that triplet. That leaves 48 percent who were Her2-negative, but they could have been any mix of estrogen and progesterone negatives and positive.

So, once again, the answer is that cancer is not one disease and may be as unique as out DNA. So, while there may be some connections between IBC and TNBC, it does not look like the two are inevitably linked.

Inflammatory breast cancer (IBC) can be difficult to diagnose, as it may show no obvious tumors. Its symptoms can seem like mastitis and some doctors may not recognize it as cancer. Instead, they prescribe antibiotics. Young women who are nursing can be at risk and should be aware that breast problems should be taken seriously.

The National Cancer Institute has a good overview of IBC.

I have had two good friends whose diagnosis of IBC required them to virtually force their doctors' hands to have them tested. Both are smart, professional woman. One is a doctor herself. Yet their doctors did not take their symptoms seriously. Both were finally diagnosed and, because they lost so much time arguing with their doctors, their cancers were advanced and required aggressive treatment. The great news: Both are healthy and cancer-free. One is 11 years past diagnosis, and one is five years out. The first had both breasts removed. The second had aggressive chemo.

Tamoxifen leads to increased risk of hormone-negative breast cancer

Even though I had estrogen-negative (ER-)  breast cancer, my oncologist was insistent that I take tamoxifen.  I refused.  And I changed oncologists. The research below supports my decision.   

Women who took tamoxifen for at least five years had more than a four-fold increased risk of estrogen-receptor negative cancer in the second breast compared to women who were not treated with hormone therapy, according to research published in the journal Cancer Research. 

The drug reduced the incidence of estrogen-receptor-positive breast cancer by 60 percent, however.

Researchers studied 367 women with estrogen-receptor-positive cancer that had also spread to the second cancer.  The comparison group was 728 women with only a primary cancer.

Some  details:

• breast cancer survivors overall who took hormonal therapy were at a reduced risk of second breast cancer.

• use of tamoxifen for at least five years reduced the risk of both estrogen-positive  and progesterone-positive breast cancer.

• use of the drug for at least five years led to increased risk of both estrogen-negative  and progesterone-negative. 

Researchers said that the reason the risk increases with longer exposure is because more time is needed  “to foster an environment that promotes estrogen receptor-negative tumor growth.”   Essentially, they said, hormone therapy gives hormone--negative cells a growth advantage.

 

SOURCE: Li, Christopher I., Daling, Janet R., Porter, Peggy L., Tang, Mei-Tzu C., Malone, Kathleen E., “Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor-Specific Subtypes of Contralateral Breast Cancer,”  Cancer Research, 2009 0: 0008-5472.CAN-09-1355. Published online August 25, 2009.