Breastfeeding, Delaying Childbirth Can Reduce Risk of TNBC

Women who wait at least 15 years after their first menstrual period to give birth to their first child may reduce their risk of triple-negative breast cancer by up to 60 percent, according to a Fred Hutchinson Cancer Research Center study.  The research also showed that breast-feeding can reduce the risk of triple-negative. The findings are published online in Breast Cancer Research and Treatment.

“Breast-feeding is emerging as a potentially strong protective factor" against TNBC, said Christopher I. Li, M.D., Ph.D., lead researcher. 

[Pat's note:  I breast fed both my children, but my oldest was born about 14 years after I started menstruating, so that part is intriguing.  Glad my daughter was older when she had her boys.]  

The study may have particular implications for some African-American women, who are disproportionately affected by TNBC but who, as a group,  are more likely to start having children at a younger age and are less likely to breast-feed, Li said.

“Our observations that delayed childbearing and breast-feeding are protective against triple-negative breast cancer suggest that variations in reproductive histories by race may to some extent explain the higher rates of triple-negative disease in African-American women,” Li said.

Researchers studied more than 1,960 Seattle-area women between the ages of 20 and 44, 1,021 with a history of breast cancer and 941 without.  

“This is an observational study and also one of the first to focus on premenopausal breast cancer and so our results require confirmation and thus should be interpreted with some caution,” Li said.

Source:  “Reproductive factors and risk of estrogen receptor positive, triple-negative, and HER2-neu overexpressing breast cancer among women 20-44 years of age,” Breast Cancer Research and Treatment. 

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Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Managing Cancer Stress + Holiday Expectations

[I wrote this last year for Breastcancer.org.  I am rerunning it with best wishes for a happy holiday season and a healthy new year.]

It’s the most wonderful time of the year, croons Andy Williams over the store’s loud speaker. Really? I think. I’m sure the retailer wants me to agree with Andy, which might mean I’ll toss some more goodies into my cart. But I am not convinced. Buying stuff does not equal happiness, nor does piped-in music mean all is wonderful. I leave the store empty-handed and head to the lake for a walk.

My post-cancer self is sort of like that — she finds less appeal in acquiring stuff and is much more eager to spend time in nature, getting exercise and some psychological balance. I like this change — I wish I had made it without having to go through surgery, chemo, radiation, and fearing for my life. I’ve learned that contentment is not for sale at the mall or on the Internet, but discontent surely is. And it is all ramped up during the holidays.

In most cases, the holidays can’t stand up to their own hype. We, in general, expect too much of the season — family togetherness, a beautiful snowy landscape, peace, joy, exquisite decorations, and fancy cookies. Our own living, breathing Hallmark card — a pretty tall order under the best of circumstances. But when you’re dealing with breast cancer, the season of forced glee can be a heavy burden.

The sadness of what a diagnosis means, the fear for our future, worry about our kids, anxiety about what treatment will do to our bodies, terror about whether or not we can beat this disease, anger that we got sick in the first place — it can be a pretty potent stew of emotions on any given day. And we’re often simply sick and tired and not physically up to our usual, let alone somebody else’s expectation of holiday-level wonderful.

My first post-diagnosis Christmas came when my hair was a thin layer of fuzz and my energy was stuck at slug level. I was still at the point where I resented every woman I saw who did not have breast cancer, so I was a little raw physically and emotionally. The only thing I really wanted that year was normalcy, which I tried to achieve by making myself at least look somewhat like the old me. I was tired of wearing wigs, so I opted for a snazzy silk scarf for a family celebration at our home. Hair equaled ordinary to me, so I wanted to show off my new stubby growth. But, for the life of me, I cannot tie a scarf like a grown-up, so that little number kept falling down my forehead or slipping lopsidedly over one ear and then another. I looked like a drunken pirate. I considered ducking into my bedroom and throwing on a wig. But, ultimately I decided that this is the way I looked at this point in my life, and my family loved me despite that fact. Or, maybe even because of it.

This should be a season of love, a time for you to rebuild your health, which may be the only gift your family and friends want. Some thoughts on making the season more enjoyable for you:

Manage Expectations. What do you need from the holidays this year? Rest? Peace and quiet? Or lots of company? Talk this over with friends and family and determine what you can and can’t do — and realize it’s OK for this year to be different. I found that decorating the house perked me up, but I still left quite a few ornaments in the basement because I simply ran out of energy. Nobody noticed.

Avoid Holiday Pitfalls. Caffeine and alcohol can take us even farther into the doldrums. Both are plentiful during the holidays and both are harmful for our physical recovery. I generally follow a diet heavy on complex carbs — grains, vegetable, and fruits — supported with cheese, yogurt, fish, and shellfish. I use the Mediterranean diet as a model, but reduce the amount of wine it suggests because of the link between breast cancer and alcohol.

Keep Active. Walk, do yoga, swim, dance — anything that keeps your body active can help calm your mind. If you feel sadness descending, or you are getting anxious, get up and do whatever you can handle: walk to the mailbox, put on a yoga DVD, or hang up the Christmas wreath. Any activity will do. A friend of mine started taking piano lessons during treatment, bought herself an inexpensive keyboard, and hit the ivories when she started feeling low. She now plays pretty darn well.

Enjoy Nature. Spending time outdoors can increase your energy and reduce your anxiety. I actually enjoy bundling up in a warm coat, hat, scarf, mittens, and boots and going out into the wintry air. Too much hot inside air can be stifling. Fresh air is invigorating for body and mind.

Honor Your Emotions. I was sad and angry that first year, grieving my former life. Pretending otherwise would have been denying my own reality. Bottled emotions, like liquor, get stronger with age. And denying them just gives them more power over you. Your body, mind, and spirit have been through a huge change, especially if you have already started treatment, and that can turn your emotions inside out. Check Breastcancer.org’s overview of treatment side effects, which includes anxiety, depression, and fatigue.

Talk it Out. If the holidays are making you especially low, find a wise friend, counselor, minister, or anybody you can trust and sit down and talk about how you feel. Sometimes simply expressing yourself is the first step toward feeling better.

Know the Difference Between Sadness and Depression. Sadness is not a sign of weakness. It is a sign you are human. Yet, if you are so sad you don’t feel like doing anything or seeing anybody, and if it’s not getting any better, you might be depressed. Depression requires professional help. But before you take any additional medications, check with your oncologist to make sure those drugs will not interfere with your treatment, especially if you are on tamoxifen.

Laugh. Watch funny movies, hang around friends who make you laugh, do anything that can tickle your funny bone. Even try laughing yoga. The act of laughing itself can reduce stress. I come from a funny family in oh so many ways, but mainly we just enjoy laughing. I know that helped my recovery greatly. And if you’re going to look like a drunken pirate in your Christmas pictures, you sure should be able to chuckle about it.

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Why Are Double Mastectomy Rates on the Rise?

From the National Cancer Institute:

New results from a population-based study show that about 75 percent of women diagnosed with cancer in one breast who chose to have a double mastectomy did so despite being at low risk of developing a new cancer in the unaffected (contralateral) breast. Greater degree of worry about cancer recurrence was associated with removing the breast not affected by cancer, known as contralateral prophylactic mastectomy (CPM).

Dr. Sarah Hawley of the University of Michigan presented the findings, from a patient survey and analysis of SEER cancer registry data, November 30 at the American Society of Clinical Oncology's (ASCO) Quality Care Symposium  in San Diego.

Only a small percentage of women diagnosed with breast cancer have clinical risk factors known to increase their chances of developing a new cancer in the unaffected breast—that is, mutations in theBRCA1 or BRCA2 genes and/or a strong family history of breast or ovarian cancer. Yet several studies, including a previous analysis of SEER data, show that rates of CPM among U.S. women with breast cancer are rising.

To investigate why women may choose CPM, Dr. Hawley and her colleagues surveyed roughly 1,500 ethnically and racially diverse women diagnosed with breast cancer that had been reported to the Detroit and Los Angeles SEER registries. Of the 564 women who received mastectomies, 107 had CPM. The remaining women had breast conserving surgery.

When the researchers compared survey responses in the two groups of women, they found that those who reported being "very worried" about recurrence were about twice as likely to have CPM as those who reported being "somewhat worried" or "not at all worried."

In addition, women who reported that they had tested positive for BRCA1 or BRCA2 mutations were about 10 times more likely to undergo CPM than those who did not have a mutation, and those having two or more first-degree relatives with breast cancer were about 4.5 times more likely to undergo CPM than those who did not have a strong family history of the disease. Although CPM reduces the risk of developing a new cancer in the unaffected breast for women with these clinical risk factors, the procedure has not been shown to reduce the risk of a recurrence of the original cancer.

"Our results suggest that many women are choosing a double mastectomy who really don't need it," Dr. Hawley said. "We want to make sure that women choose CPM…with a good, clear understanding of what it's doing and not doing in terms of risks and benefits…. What you do is a personal decision, but it should be an informed one."

Dr. Hawley and her colleagues are still analyzing the survey data and have not yet examined some other possible reasons that women may be opting for CPM.

"This study suggests that we should re-examine how we communicate with our patients regarding the decision of whether to undergo prophylactic mastectomy," said Dr. Jyoti Patel, an oncologist at Northwestern University who moderated a November 30 ASCO press briefing at the symposium.

This study was funded by NCI (CA088370 and CA109696).

Further reading: "Preventive Double Mastectomies Increasing Despite Some Concerns"

More Genomic Sequencing Research Leads to Targets for Metastatic TNBC

NEWS RELEASE FROM TGEN

PHOENIX, Ariz. — Dec. 6, 2012 — Genomic sequencing has revealed therapeutic drug targets for difficult-to- treat, metastatic triple-negative breast cancer (TNBC), according to an unprecedented study by the Translational Genomic Research Institute (TGen) and US Oncology Research.

The study is published by the journal Molecular Cancer Therapeutics and is currently available online. 

By sequencing, or spelling out, the billions of letters contained in the genomes of 14 tumors from ethnically diverse metastatic TNBC patients, TGen and US Oncology Research investigators found recurring significant mutations and other changes in more than a dozen genes. In addition, the investigators identified mutations previously unseen in metastatic TNBC and took the sequencing data into account in selection of therapeutic protocols specific to each patient’s genetic profile.

“This study stands as a one-of-a-kind effort that has already led to potentially beneficial clinical trials, and sets the stage for future investigations,” said Dr. John Carpten, Ph.D., TGen’s Deputy Director of Basic Science and Director of TGen’s Integrated Cancer Genomics Division, and the study’s senior author.

The most frequently mutated gene among the tumors (seven of 14) was the TP53 tumor suppressor, and aberrations were observed in additional tumor suppressor genes including CTNNA1, which was detected in two of six African American patients (who typically have more aggressive and treatment-resistant disease). Alterations were also seen in the ERBB4 gene, known to be involved in mammary-gland maturation during pregnancy and lactation, but not previously linked to metastatic TNBC.
The study included an “outlier analysis,” which assessed expression patterns for each tumor when compared against the other tumors examined in the study. Specific cancer genes overexpressed among tumors in the study’s cohort included: ALK, AR, ARAF, BRAF, FGFR2, GLI1, GLI2, HRAS, HSP90AA1, KRAS, MET, NOTCH2, NOTCH3, and SHH. Significantly underexpressed cancer genes included: BRCA1, BRCA2, CDKN2A, CTNNA1, DKK1, FBXW7, NF1, PTEN, and SFN.

Each tumor was genomically unique, but nine of the 14 contained alterations in one or both of two particular cellular pathways: RAS/RAF/MEK/ERK and PI3K/AKT/MTOR. Targeted therapeutic intervention aimed at these pathways achieved impressive responses in several cases.
“Importantly, the analysis provided insights into the potential unique therapeutic vulnerabilities of each cancer,” said Dr. Joyce O’Shaughnessy, M.D., the study’s other co-lead author. Dr. O'Shaughnessy is a practicing oncologist with Texas Oncology — an affiliate of The US Oncology Network — and is the Celebrating Women Chair of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center.Metastatic TNBC is a highly aggressive form of breast cancer that disproportionately affects African-Americans. It is called triple-negative because tumors do not express the estrogen receptor, progesterone receptor or HER-2, the biomarkers successfully targeted in most breast cancers.
Metastatic TNBC also has a poor prognosis once the cancer has spread to other organs, with a median survival rate among metastatic patients of only one year. While TNBC accounts for only about 15 percent of all breast cancers, its more aggressive biology makes it responsible for nearly one in four deaths related to this disease.
“The nature of this disease cries out for innovative research techniques such as whole genome sequencing coupled with new tools for data analysis,” said Dr. David Craig, Ph.D., TGen’s Deputy Director of Bioinformatics, and one of the study’s co-lead authors.

“We are aware that these results are preliminary and based on a small series of patients,” said Carpten. “However, our study will pave the way for new clinical trials and novel hypotheses for future testing in a very difficult to treat cancer.”

SABCS: San Antonio

We al worked hard at the San Antonio Breast Cancer Symposium.  But the weather was gorgeous and the convention was right on the river walk, so we had a gorgeous place to unwind.  It was difficult to remember that it is only 17 days to Christmas—until you see the Alamo all decked out.   The river walk was full of sparkling lights at night, but all the photos I took looked a bit too psychedelic to share.

SABCS: A Recap of Triple-Negative Research

The best news from the 2013 San Antonio Breast Cancer Symposium is its emphasis on triple-negative breast cancer.  There are so many papers presented on the subject that I can’t keep up. Those of us who have been hanging around this dance for a long time—I was diagnosed in 2006—remember the frustration of seeing and hearing little about this disease from researchers and nothing from the media, who simply didn’t appear to comprehend the complexity of breast cancer as a whole and were unaware that there was a type not fueled by estrogen or progesterone.  And Her2?  What’s that?

That is changing.  More than 82 clinical trials are now looking for targeted treatments for TNBC.  Because TNBC is defined by what it lacks—receptors for estrogen, progesterone and her2/neu—it also lacks a targeted therapy.   Researchers are busy finding a genetic signature of subsets of TNBC that will lead to those therapies.

The San Antonio symposium this year had at least 20 papers looking at the genetics of TNBC, its response to chemo, and the potential for those targeted drugs, which no longer look as elusive as they had once been.

The highlights of research presented on TNBC this year:

Androgens

Some 75 percent of all breast cancers and 10 to 20 percent of triple negative cancers are positive for the androgen receptor. Several research studies have looked at the influence of androgen receptors on TNBC, which means new treatments plus a broader and deeper understanding of the disease.  TNBC cancers that are also positive for androgen receptors are molecularly similar to prostate cancer and could potentially be treated similarly. 

AR-positive tumors responded well to bicalutamine and to 17-DMAG, a drug that has been recently in clinical trials, according to research presented by Jennifer Pietenpol, Ph.D., director of the Vanderbilt-Ingram Cancer Center. 

A phase I clinical trial at the University of Colorado has been studying the effectiveness of enzalutamide, a drug used to treat prostate cancer, on triple-negative. A phase II trial is planned at CU, Memorial Sloan-Kettering Cancer Center and the Karmanos Cancer Institute.

A Heterogeneous Disease

It is increasingly clear that TNBC is not one disease, but a family of diseases, some of which are highly aggressive, and some that are not aggressive at all.  We’re getting increasingly closer to knowing which ones are which. 

"This heterogeniety highlights the need for personal medicine," said Justin M. Balko, Pharm.D, Ph.D., research faculty in the laboratory of Carlos Arteaga, M.D., at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. Balko’s research looked at how TNBC tumors changed genetically after neoadjuvant chemotherapy, and highlighted frequent mutations and amplifications, including the novel JAK2 genetic mutation, that can lead future research and the development of TNBC-specific drugs. 

The JAK2 gene has not been observed in previous research,  Balko said. The patients in the study who had the JAK2 amplification tended to have a poor prognosis, which means that JAK2 may be a key to which cases of TNBC are aggressive and which aren’t.  Those with JAK2 expression may respond to inhibitors currently in clinical trials for inflammatory diseases, Balko said, which could be a game changer.  

In both Pietenpol and Balko’s presentations, each TNBC tumor was unique, with different mixtures of similar mutations and amplifications. While TNBC tumors might share a tendency toward specific genetic mutations, the way those mutations play out differs from tumor to tumor, and may even change during treatment.

Both studies showed a frequent mutation of the TP53 tumor suppressor in TNBC tumors.

Response to chemotherapy

Breast cancer might be biologically different in very young women versus older women, according to Sibylle Loibl, M.D., Ph.D., associate professor at the University of Frankfurt in Germany.  This may explain why younger women tend to respond better to neoadjuvant chemotherapy than older women, achieving a complete pathological response  more often that older women.  A compete pCR is associated with a much better prognosis.

And in a phase III multicenter study. women with metastatic triple-negative breast cancer had a more significant response to treatment with eribulin versus capecitabine, with a median overall survival of 14.4 months with eribulin compared with 9.4 months with capecitabine.  The survival line for metastatic TNBC extended beyond six years.

Most Women Survive

The great majority of women with local and regional recurrences survive after five years with proper treatment.  Women with estrogen-negative breast cancer benefitted the most if that treatment included chemotherapy after surgery, according to the Chemotherapy as Adjuvant for Locally Recurrent Breast Cancer (CALOR) trial.  Researchers reported a 67 percent  disease-free survival rate after five years for those who received chemotherapy, versus 35 percent for those who did not and a 79 percent overall survival rate after five years for those who received chemotherapy and 69 percent for those who did not. A big takeaway here is that local and regional recurrences—near the site of the original primary tumor and in the lymph nodes—are highly treatable.

In the BEATRICE phase III trial ,  some 87 percent of TNBC patients with stages 1, 2, and 3 triple-negative breast cancer treated with current chemotherapy survived disease-free.  

Such positive results are becoming common for TNBC, said Kent Osborne, M.D., director of the Dan L. Duncan Cancer and the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston, Texas.  “We’re seeing this across the board.”

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

SABCS: Women with TNBC more sensitive to eribulin

Women with metastatic triple-negative breast cancer had a more significant response to treatment with eribulin (Halaven) versus capecitabine (Xeloda) than women with other forms of breast cancer, with a median overall survival of 14.4 months with eribulin compared with 9.4 months with capecitabine.  The results were part of a phase III multicenter study presented today at the San Antonio Breast Cancer Symposium.

The median overall survival for all patients assigned to eribulin was 15.9 months compared with 14.5 months for patients assigned to capecitabine. Median progression-free survival was 4.1 months for eribulin and 4.2 months for capecitabine. 

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!