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.

African-American Women May Refuse Important Treatments for Triple Negative

One in four African American women with late stage breast cancer refused chemotherapy and radiation therapy, says research to be published in the July 1, 2009 issue of Cancer, a  journal of the American Cancer Society.

Researchers reviewed stage III breast cancer data from 2000 to 2006 from an inner city hospital in Atlanta that serves a large African American population.

They identified 107 cases diagnosed, treated or both from 2000 to 2006. Roughly 87 percent of these cases were in African American women; 29 percent of all cases were triple negative.

• 20.5 percent of patients with stage III breast cancer refused chemotherapy.

• 26.3 percent who should have received chest radiation refused.

• There was no difference in marital status, religious background, or age of the patients who refused either chemotherapy or radiation compared with the patients who received recommended care.

Why did some women refuse care?  Researchers aren’t sure why, but they speculate that a range of factors could be involved:  socioeconomic and demographic factors, cultural beliefs, healthcare access, additional illnesses, and patient choice.  

But here’s the neat part:

As a result of the study, researchers have implemented a community outreach program that includes a nurse practitioner and a social worker who follow all patients throughout their cancer treatments, ensuring that they get proper care.  All women should have this sort of resource, but this is a good beginning.

Source:   “Characteristics and treatment modalities for African American Women diagnosed with Stage III breast cancer.” Monica Rizzo, Mary Jo Lund, Marina Mosunjac, Harvey Bumpers, Leslie Holmes, Ruth O’ Regan, Otis W. Brawley, and Sheryl Gabram. CANCER; Published Online: May 22, 2009 (DOI: 10.1002/cncr.24334); Print Issue Date: July 1, 2009.

Risk factors for triple negative breast cancer

The Life After Cancer Epidemiology (LACE) Study underscores what other research has demonstrated: women with triple negative breast cancer are more likely to:

• be younger at diagnosis
• African American
• overweight and/or obese at diagnosis if premenopausal

The were less likely to breastfeed for long periods—more than four months—and were more likely to not breastfeed if they had at least three children.

The study consisted of 2280 women diagnosed with invasive breast cancer (stages I, II, or IIIA) between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California Cancer Registry and the Utah Cancer Registry. They were between 18 and 70 years old and between 11 and 39 months post-diagnosis, free of recurrence, and with no history of other cancers in the five years prior to enrollment.

Tumor subtypes the used and the percentage in that group:

Luminal A: ER positive and/or PR positive, and Her2 negative (73.4%)
Luminal B: ER positive and/or PR positive, and Her2 positive (11.6%)
Triple negative: ER negative, PR negative, and Her2 negative (11.3%)
Her2-overexpressing: ER negative, PR negative, and Her2 positive (3.7%)

Luminal B cases were more likely to be younger at diagnosis and were less likely to consume alcohol or use hormone replacement therapy.

Her2-overexpressing cases were more likely to be younger at diagnosis, less likely to use hormone replacement therapy, and Hispanic or Asian.

Some other interesting stats:

•The majority of the whites (75.3%), Asians (71.4%), Hispanics (68.5%), other (68.5%), and African Americans (59.4%) had luminal A tumors.
• Her2-overexpressing tumors were least common among all races/ethnicities (whites 3.1%, African Americans 3.2%, Asians 6.4%, Hispanics 6.6%, other 5.5%).
• African Americans had the highest prevalence of the triple negative subtype (28.4%) compared with the other races/ethnicities (whites 10.5%, Asians 6.3%, Hispanics 10.7%, other 13.0%).
•African Americans (average age: 56.2) and Asians (average:54.8 years) were more likely to be diagnosed at a younger age.
•Whites were more likely to be diagnosed at an older age (59.8).
•, Asians (59.1%) were less likely to be post-menopausal than whites.
(75.6%), African Americans (71.4%), and other races/ethnicities (72.9%).
• A family history of breast cancer was more common among whites (22.6%) and other
races/ethnicities (24.1%), than among the other groups.
• African Americans and Hispanics had more biological children and were younger during their first pregnancy.
• Whites were more likely to have consumed alcohol while Asians were more likely to have never smoked.
• More whites had used HRT (76.2%).
• Fewer Asians (44.1%) had used oral contraceptives.
• African Americans were more obese at diagnosis.

The study was published in the May 2009 Breast Cancer Research, an open access journal. Download a PDF here.  Or read the abstract.


SOURCE: Kwan, ML, Kushi, L, Weltzien,E, Maring, B, Kutner, S, Fulton, R, Lee, M,Ambrosone, C, Caan,B,  “Epidemiology of breast cancer subtypes in two prospective cohort studies of
breast cancer survivors,” Breast Cancer Research, 2009, 11:R31. 

Bisphosphonate may benefit metastatic hormone negative breast cancers

According to research in the open-access journal,  BMC Cancer, patients with hormone-negative cancer with bone metastases may  benefit from bisphosphonate (BP) treatment.  Of the 317 patients followed, 230 (72.6%) had hormone positive breast cancer and 87 patients (27.4%) had hormone negative.  

Patients with hormone-positive breast cancer showed no benefit from BP.  Those with hormone-negative,  however, showed what researchers called "significant prolonged survival" from the drug. Disease-free survival was more than two years, with fewer than three metastatic sites.  Patients received an average of 17.7 cycles of BP.

Download a PDF of the research here.

New study planned for hormone-negative therapies

Aragon Pharmaceuticals has raised $8 million to discover and develop new therapeutics for the treatment of hormone-negative cancers, with an initial focus on prostate and breast cancer.

The company has been involved in recent discoveries that show that the biology of hormone-negative cancers can be overcome through the creation of a new class of nuclear receptor targeting drugs.

The company will focus on androgen and estrogen receptors.

Read the company's news release here. 

DEAR1 gene could explain triple negative breast cancer

Researchers at the MD Anderson Cancer Center say a newly identified gene, DEAR1, may serve as a biomarker for high risk of local recurrence, especially for younger women with triple negative breast cancer.

They studied tissues from tumors of 123 women whose breast cancer began between ages 25 and 49 and advanced to invasive disease.  Of these, 56 percent had lost DEAR1  ((ductal epithelium-associated ring chromosome 1) expression.  This correlated with a family history of breast cancer and with triple-negative disease.

 

• 58 percent of those without DEAR1 were local recurrence-free survival 15 years after surgery. 

• 95 percent of those with DEAR1 expression were local recurrence-free at 15 years.

The authors suggested that measurement of DEAR1 expression “could be an important marker to stratify early-onset breast cancer patients for increased vigilance in follow-up and adjuvant therapy.”

"The correlation with local recurrence is significant because so many young women have recurrences in the breast, and cancers that do recur tend to be more aggressive," said senior author Ann McNeill Killary, Ph.D., professor in M. D. Anderson's Department of Genetics. "Young age has been considered a risk factor for local recurrence and metastasis. It is important to understand the genetic mechanisms operating in early-onset breast cancer and to determine whether there is a way to identify young women who might be at a higher risk of recurrence."

Read more about the research here.

Three Years Cancer Free

Mammogram: Clear.

Chest X-Ray:  Clear.

Blood tests: Clear.

Symptoms: None.

Yeaaaaaaaaaaaaaaaaaaa!!!!!!!!!!!!!!!!  I reached my third-year anniversary cancer-free.  And, as those who know hormone-negative breast cancer understand, the third year is the biggee.  My chances of recurrence go way down now.  Because this is an aggressive cancer, recurrences hit between one and three years after diagnosis and decline rapidly after that.

I am a happy woman.  And thankful.

Standard chemotherapy more effective than capecitabine for older women

Older women with early-stage triple negative breast cancer had four times the chance of relapse if they were treated with the chemotherapy drug capecitabine (Xeloda ) rather than standard chemotherapy, either cyclophosphamide/methotrexate/fluorouracil, or doxorubicin/cyclophosphamide. Their risk of death was three times higher, according to data published in the May 14 issue of The New England Journal of Medicine.

Capecitabine is taken orally.

Women 65 and older were randomly assigned to standard chemotherapy or capecitabine . Among the patients in the standard chemotherapy group, 133 chose cyclophosphamide/methotrexate/fluorouracil, 184 chose doxorubicin/cyclophosphamide and nine withdrew without choosing a treatment.

CMF was administered in standard doses for six cycles repeated every six weeks.

AC was administered in standard doses for four cycles repeated every three weeks.

Capecitabine was administered in two divided doses for 14 consecutive days every three weeks for six cycles. 

Patients were evaluated at an average of 2.5 years. For all women regardless of receptor status, those in the capecitabine group had double the risk for recurrence and a similar risk for death. Breast cancer was the most common cause of death in the capecitabine group compared with other cancers or cardiovascular disease for patients in the standard chemotherapy group. 

But when women were further evaluated by receptor status, those in the triple negative group fared even worse, with four times the risk of recurrence and three times the risk of death.

Standard chemotherapy also resulted in increased estimated three-year relapse-free survival (85 percent vs. 68 percent) and overall survival (91 percent vs. 86 percent) compared with capecitabine for all women, regardless of hormone status.

Androgen receptors: a new category of triple negative breast cancer?

Another receptor—the androgen receptor—is being studied to help evaluate the aggressiveness of breast cancer tumors and how they react to treatment

“I think we are seeing the birth of a new concept in breast cancer—the androgen-receptor-positive breast cancer,”  says Jose Baselga, M.D., co-chair of the Impakt Breast Cancer Conference in Brussels, Belgium. “This is an important development in finding new targets that we can attack with new drugs in the future.”

Baselga was responding to research presented at the conference on the effects of androgens on chemotherapy.  Patients  who were triple negative breast and who also had androgen receptors tended to react less favorably to chemotherapy than those without the receptors.

This is more evidence of what doctors have been saying for some time:  Cancer is many diseases.  It is important to understand that triple-negative is also more than one disease.  That explains why I was lucky enough to celebrate my third post-diagnosis year cancer-free, while my friend Karen had a recurrence.  I suspect that, even though our diseases were in the same general category of hormone-negative, they were significantly different and I lucked out.

A clinical trials is now underway to target these receptors, with the hopes of using it for prognosis and the development of drug therapy.

The Impakt conference was sponsored by the European Society for Medical Oncology May 7-8, 2009.

 

 

From Dr. Susan Love: "Is TNBC Getting a Bad Rap?"

On the Dr. Susan Love Research Foundation blog, Dr. Love gives a succinct overview of what's happening with triple negative breast cancer research, noting that docs are taking the disease seriously and "help is on the way." (Hurry!)   Check it out. 

Triple Negative Breast Cancer Isn’t Always Deadly

Research at the New York University School of Medicine demonstrates that a diagnosis of triple negative breast cancer (ER-, PR- and Her2-) is not always lethal.  Researchers studied 145 triple negative tumors and found:

•  About 23 percent were moderate or low-grade.

• 11 were low grade, 23 were moderate grade, and 111 were high grade.

• Of the low grade lesions, only one had spread to the lymph nodes.

• Of the medium grade lesions, five had spread.

• Of the high grade lesions, 37 had spread.

"Our preliminary results show that triple negative breast cancers are a heterogeneous group. Although many are high grade lesions, some are moderate or low grade demonstrating a lower rate of lymph node metastasis," said Cecilia Mercado, M.D., an author of the study.

The research was presented at the American Roentgen Ray Society annual meeting, April 14, 2008.

Source:  " Does Histologic Grade Correlate with Nodal Status in Triple-Negative Breast Carcinoma? " Vieira, C. , Mercado, C., Guth, A., Moy, L.,Toth, H., Cangiarella, J.  American Journal of Roentgeonology. 190:A17-A21. 2008.

 

Triple Negative Survivor Story: Josie Garcia

Josie Garcia of Sacramento, California, shared her two-year survival story and positive personal philosophy—after a diagnosis of stage III triple negative—in the Sacramento Press:

Every day we hear of survival stories that stretch as far as distant, war-torn countries. Closer to home, we hear the story of the immigrant, of those rooted in our impoverished neighborhoods, of those affected by the current recession.

Survival is an opportunity at the turn of every day. For the sound-minded, those opportunities rank upwards till reaching the most important meaning for us: life. A life-threatening opportunity is when life grabs hold of your soul and knocks your senses so straight you never realized there was more to life in the "most" way.

Welcome to my survival story, one that has become more common due to medical breakthroughs and outreach. I am a breast cancer survivor. Just before the summer of 2007, at the age of 39, and as a single Mom to a 2-year-old boy, I received a shocking diagnosis: Stage III, triple negative breast cancer, tumor range six to nine centimeters with three enlarged lymph nodes.  Read more