PARP Inhibitors May Help More Than Triple Negative

I’ve written about PARP inhibitors recently, but they’re back in the news. 

Patients with cancer genes—BRCA1 and BRCA2—have been shown to react positively to a type of PARP inhibitor, a drug called olaparib.  In a small but significant study, olaparib was successful in shrinking breast and prostate cancer tumors, with some disappearing entirely.  The study was reported in the New England Journal of Medicine.

Read more about it here.

PARP is short for poly (ADP-ribose) polymerase, an enzyme used by cancer cells to repair DNA damage.

 

 

Herceptin May Be Effective Drug for Hormone Negative Breast Cancer

The drug commonly used for Her2-positive breast cancers may actually turn ER-negative status into positive. It’s a two-step process, though, and the research was done on ER-negative, Her2-positive laboratory cells, not on human subjects.  Still, it offers amazing potential and could ultimately provide much-needed therapy for hormone-negative breast cancer, including triple negative.

After being treated with trastuzumab (Herceptin), ER-negative cells actually turned into ER-positive cells, making them then react to anti-estrogen drugs like tamoxifen and aromatase inhibitors, according to research presented at the Endocrine Society meeting this month.

The research was done in vitro—in a lab, on existing cells, rather than in human subjects. Cells were ER-negative, Her2-postive and  were treated with  trastuzumab; after 72 hours they were treated with the hormones estradiol  and androstenedione.  After that they were given aromatase inhibitors and antiestrogens.

The tumors then reacted in much the way ER-positive tumors do to aromatase inhibitors and antiestrogens.

Read more about the study here.

SOURCE: Sabnis G, Brodie A "Trastuzumab sensitizes ER negative, HER-2 positive breast cancer cells (SKBr-3) to endocrine therapy" ENDO 2009; Abstract OR38-02.

Oral Contraceptives Increase the Risk of Triple Negative Breast Cancer

Women under the age of 40 who used oral contraceptives increase their risk of triple-negative breast cancer by more than 2.5 times, according to research in Cancer Epidemiology Biomarkers and Prevention (April, 2009).   There was no increase in the risk for hormone-positive breast cancer.

 

 

Scientists study protein linked to triple negative

The protein EZH2 is found in a great majority (74 percent) of hormone-receptor-negative tumors, mostly in triple negative. It is linked to larger tumor size—over 2 cm—and affected lymph nodes, according to research presented at the 2009 annual meeting of the American Society of Clinical Oncology.

Researchers speculate that EZH2 could ultimately be much-needed therapy for women with hormone-negative breast cancer. The study is continuing with the goal of determining EZH2's role in survival of hormone-negative cancer.

More perspective on PARP inhibitors for triple negative

An expansion on my previous post on PARP inhibitors:

A Curetoday.com blog gives a bit more explanation on the recent research (presented at the American Society of Clinical Oncology annual meeting)  showing how PARP inhibitors can help advanced triple negative breast cancers:

What happens when a preliminary study that was not designed for drug approval ends up showing dramatic results?

A study in patients with advanced "triple negative" breast cancer (defined as being negative for estrogen, progesterone, and HER2 receptors) compared chemotherapy (Gemzar and carboplatin) with or without BSI-201, a poly ADP-ribose polymerase (PARP) inhibitor.

PARP inhibitors have been shown to work exceptionally well in the laboratory against cancers that have defects in DNA repair – this is an abnormality that is prominent in cancers that derive from patients who have inherited mutations in the breast and ovarian cancer predisposing genes BRCA1 and 2. It turns out that BRCA1-associated tumors tend to be triple negative (although not all triple negative tumors have abnormalities of the BRCA pathways).

This was a preliminary phase II study, so even though it was randomized, it did not have enough patients to qualify as an FDA-approval trial. But it nevertheless showed unprecedented effects on inducing tumor responses, delaying time to progression, and improving survival – even greater than hormonal therapy and Herceptin have.

Read the entire article here.

Two stories of women coping with triple negative

From the Grand Island (NE) Independent:

“We’re a package deal.”

That’s how Heather Gideon describes her relationship with Angie Huxtable.

So when Huxtable agreed to be in today’s style show for the annual Cattlemen’s Ball of Nebraska, Gideon said, there was absolutely no question she would appear on the runway as well.

The style show is just one of the many activities that will help raise money for cancer research as part of the 2009 

Cattlemen’s Ball, which has a goal of collecting $1 million.

Whatever amount is raised will go to the UNMC Eppley Cancer Center and local health care organizations.

That money for research is important to both Wood River women, who were each diagnosed with breast cancer in May 2007.

While Huxtable remains cancer free, Gideon’s cancer re-emerged just months after her initial round of treatment was finished. Gideon is now diagnosed with Stage 4 breast cancer.

“I’ve been given one to four years to live,” said Gideon, who noted there is no current treatment that doctors say will cure her cancer.

Treatments now are designed to hold the cancer at bay.

Read the entire article here.

Another Triple Negative Survivor Story

From the Albany (NY) Herald online:

Hope and healing are often found in the unlikeliest of places. Breast cancer survivor Candy Reid found source of hope in a circle of tubing better known as the hula hoop.

Reid is the founder of Hoops for Healing, a online business that sell hula hoops custom made by Reid and her family.

She said that she cannot believe how the business has taken off and that the journey from battling cancer to operating a successful business was as circular as the hoops she now makes from her home in Albany.

"What came from this horrible experience is amazing to me," said Reid. "I've grown a lot, I've changed a lot. God has really been able to show his goodness through so many ways."

She said that before hearing the terrible news that she had breast cancer in December 2007, she was a busy housewife dedicated to home schooling her four children.

"I am really dedicated to my family and they have been so supportive through all this," Reid said.

She said that she was diagnosed with triple negative breast cancer, a specific subtype of cancer that is clinically characterized as more aggressive and less responsive to standard cancer treatments.

"I immediately began chemotherapy treatments which ended in May 2008 and then I had a bilateral mastectomy in June 2008," Reid explained. "This was followed by seven weeks of radiation."

Read the entire story here.

Your Nurse Can be Your Advocate

In the confusing days and weeks after a breast cancer diagnosis, a nurse navigator or patient advocate can help you make sense of your disease and its treatment and even guide you in getting a second option.  Nurse navigators follow cancer patients from diagnosis through follow-up care and help make sense of the doctors, treatments, jargon, and options while providing a supportive presence.  In most cases, navigators collaborate with all members of the medical team; educate and counsel patients and their families; and coordinate care with oncologists, surgeons, pharmacists, dieticians, and counselors. 

Check to see if your healthcare provider offers access to such a professional.  If not, lobby for them to start.  We all need more information than we have after a breast cancer diagnosis.  We should not be left to our own devices to figure it all out.

 

Cancer-Fighters in Your Kitchen

Stock your cupboards and fridge with tasty cancer fighters. A diet rich in fruits and vegetables and low in fat is the recipe for breast health, according to numerous studies:

• Whole grain breads and cereals fortified with B vitamins, especially folate. Folate is important in fighting hormone-negative breast cancer.

• Cruciferous vegetables: broccoli, cauliflower, cabbage, kale. These are high in Indole-3-Carbonale (I3C) that has been shown to have anti-cancer properties.

• Fruits and vegetables, especially brightly colored. Red and purple plants—red cherries, blueberries, acai—are high in anthocyanins, which are potent antioxidants.

•  Green tea, which contains plant chemicals called catechins, a plant chemical that may inhibit the invading capacity of breast cancer cells.

•  Flaxseeds, which contain cancer-fighting lignans.

• Organic foods when possible, especially dairy products. Organic food is grown or produced without the use of pesticides, fertilizers, antibiotics or growth hormones, all of which are implicated in breast cancer.

It’s Not a One-Size-Fits-All Disease: Breast Cancer Myths

MYTH 1:  Breast cancer is always fatal. fact: The great majority of women with breast cancer go on to live long and meaningful lives.  Ninety-three percent of the women with the most common type, hormone-positive, are disease-free at five years.  

MYTH 2:  There’s always a tumor. FACT:  two types—lobular and inflammatory—may have no lumps.  Women with lobular often have thickening of the breasts; those with inflammatory usually have red, swollen breasts, often with a pitted appearance.  

MYTH 3:  Estrogen is always the culprit. FACT: there’s a form of breast cancer that most often strikes young women, that is not fueled by estrogen.

MYTH 4:  Tamoxifen or Arimidex are for everybody.  FACT: women with estrogen-negative disease get no benefit from these drugs, which are estrogen blockers.   This is especially important, as these drugs have significant side effects, one of which is an increased risk of other cancers.

A Weight-Loss Strategy That Works: Your Friends

OK, so you know losing weight can improve your chances of fighting cancer, but how can you focus on weight loss when you’re fighting for your life after a cancer diagnosis?   Ask friends to help. Research (New England Journal of Medicine, July 2007) shows that we lose weight more effectively if we belong to a social network in which others are also losing. So, when friends and family ask what they can do for you, give them an option that helps their health as well. Work together to change your diet and increase your physical activity.  

• Make a formal diet and exercise plan and publicize it. Going public makes it harder to fall off the wagon.

• Don’t diet—change the way you eat. This is not a short-term goal, but a long-term change. And your family will benefit from a healthier diet as well—you will be helping them reduce their cancer risk.

• Have healthy potlucks. Show off your low-calorie, low-fat, low-cholesterol recipes and show one another that you can still enjoy food together.

• Pool your money to hire a dietician. Most cancer clinics have access to these professionals.
 

• Create your own gym group with a personal trainer.

• Have fun—get a dance video game, round up the kids and boogie the pounds away.

Your Best Way to Fight Breast Cancer: Lose Weight

Maintaining a healthy weight is crucial to avoiding breast cancer, fighting it once you’ve been diagnosed, and reducing its risk of recurrence. Yet most cancer patients are overweight and few know of the relationship between weight and cancer. Some stats:

• Women who gained 55 lbs. or more after age 18 had almost 1½ times the risk of breast cancer compared with those who maintained their weight, [July 12, 2006, issue of the Journal of the American Medical Association.]

• Many doctors reduce the levels of chemotherapy for obese women, potentially hurting their chances of survival, according to research at the University of Rochester Medical Center.

• Breast cancer survivors who ate a low-fat diet—of 32 grams a day, or roughly 20 percent of the daily allotment of fat— lowered their risk of recurrence, in some cases by an impressive 42 percent, according to the Women’s Intervention Nutrition Study (WINS).

• Canadian researchers discovered that breast cancer survivors, for the most part, have a surprisingly unhealthy lifestyle, being obese and low on physical activity. [June 1 2008 issue of Cancer, the journal of the American Cancer Society.]

• A majority of women in a recent study were unaware that being overweight increased their cancer risk. [October 2008, Obstetrics and Gynocology.]

New drug being tested for triple-negative breast cancer

News from the 2009 annual meeting of the American Society of Clinical Oncology:  PARP inhibitors continue to be a promising line of attack for triple negative.  In a study presented at the conference on a new drug, BS-201, which includes a PARP inhibitor:

•  of 116 women with advanced triple-negative breast cancer, those who received the drug in addition to standard chemotherapy lived a median of 9.2 months, compared with 5.7 months for those who received only the chemotherapy. 

• PARP inhibitors block the action of an enzyme that helps repair DNA. Without the ability to repair their DNA, tumor cells can die or more easily be killed by chemo.

• BS-201, was developed by BiPar Sciences  that was acquired in April by Sanofi-Aventis.  AstraZeneca is also developing PARP inhibitors.