Cisplatin Again Shows Promise As TNBC Treatment

The chemotherapy drug cisplatin may be effective against triple-negative breast cancer, especially those related to the BRCA1 gene. As reported in the Journal of Clinical Oncology (January 25, 2010), researchers treated 28 women with stage II or III with TNBC with four cycles of 75 mg of cisplatin every 21 days. The women then had surgery and radiation, based on the assessment of their individual doctors. Of the 28 women:

• 6 achieved pathologically complete response, which has been associated in previous studies with long-term reduction in recurrence. This included women with the BRCA1 gene.

• 18 had a clinical complete or partial response, also a positive sign for long-term health.

• 4 showed a progression of the disease.

Younger women showed a better response to the drug, as did women with low BRCA1 expression.

An earlier study published in the Annals of Oncology also showed positive results with cisplatin.

I blogged about cisplatin, doxorubicin, cyclophosphamide (4HC), and docetaxel on TNBC tumors and on Italian trials using cisplatin, epirubicin, and paclitaxel (PET).

Clinical trial of PARP Inhibitors open to TNBC patients

From a news release from the Baylor College of Medicine:

HOUSTON -- (January 25, 2010) -- Breast cancer patients who have triple negative breast cancer, an aggressive form of the disease, that has spread to other parts of the body, are being asked to participate in a clinical study of a promising new treatment called PARP inhibitors.

Researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine will conduct the study at both the Baylor Clinic and the Harris County Hospital District's Ben Taub General Hospital.

“This is a very important study,” said Dr. Mothaffar Rimawi, assistant professor in the Smith Breast Center and the principal investigator of the study. “This type of cancer does not have many therapeutic options, other than standard chemotherapy, and is associated with a very poor chance of recovering when the disease has spread to other parts of the body.”

Early results promising

DNA repair is an important process to maintain healthy cells. Cancer cells use this process to repair their DNA as well. However, in cancer cells, this process can be defective and the cancer cells become more dependent on an enzyme called PARP to repair their DNA.

There are multiple signaling pathways in normal cells. PARP inhibitors work by blocking the DNA repair signaling pathway, causing the cancer cell to accumulate DNA defects and die.

Very promising results from an early stage PARP inhibitor study were announced at the American Society of Clinical Oncology’s annual meeting in May 2009.

“In this randomized trial, there was a significant advantage in terms of progression-free survival in patients taking chemotherapy plus PARP inhibitors versus patients taking chemotherapy alone,” said Rimawi. Progression-free survival indicates the length of time in which the patient lives without cancer growth following treatment.

Phase III

The current study, a Phase III study, will be part of a national, multi-center, randomized trial using the same structure as the previous study.

This study hopes to better define those promising results in a large group of patients, Rimawi said.

The study will evaluate response in patients taking chemotherapy alone versus patients taking a combination of chemotherapy and PARP inhibitors.

“Patients getting chemotherapy alone will be switched over to the PARP inhibitor if the chemotherapy is not working so everyone will have a chance at receiving the new drug,” said Rimawi.

Study criteria

Interested participants must:

• Be diagnosed with stage four, metastatic (cancer spreading to other body parts) triple negative breast cancer
• Be female over the age of 18
• Not be pregnant or breastfeeding
• Have no other diagnosis of cancer five years or more in the past, with the exclusion of non-melanoma skin cancer
• Have no prior treatment with PARP inhibitors or the following treatments: gemcitabine, carboplatin, cisplatin.

For more information on this study or to enroll, please contact BCM coordinator Claudette Foreman at 713-798-7315 or caforema@bcm.edu.

The New York Times Examines Radiation Effects--and Mistakes

The New York Times is examining the effects of radiation. Read the first in the series here--and if you are due for radiation, make sure you ask your radiation oncologist for the safety procedures used at your facility.

As Scott Jerome-Parks lay dying, he clung to this wish: that his fatal radiation overdose — which left him deaf, struggling to see, unable to swallow, burned, with his teeth falling out, with ulcers in his mouth and throat, nauseated, in severe pain and finally unable to breathe — be studied and talked about publicly so that others might not have to live his nightmare.

Sensing death was near, Mr. Jerome-Parks summoned his family for a final Christmas. His friends sent two buckets of sand from the beach where they had played as children so he could touch it, feel it and remember better days.

Mr. Jerome-Parks died several weeks later in 2007. He was 43. Read the entire article here.

Socially isolated women more prone to triple-negative

Researchers at the University of Chicago have isolated another factor in triple-negative breast cancer: social isolation. They found that women living in a high crime area of Chicago are more likely to develop triple-negative, which is more prevalent among African-Americans. Loneliness and a lack of social outlets, they say, lead to a surge in the stress hormone cortisol, which allows tumor cells to grow through efficient use of sugar and fat. And sugar and fat are out to do no good—they’re both associated with aggressive cancers.

Women with triple-negative also had consistently low cortisol levels, leading to a flat reaction to stress, again a result of life in a high-crime neighborhood, according to the study, which was published in the Proceedings of the National Academy of Sciences.

But, women with a strong social network were more likely to fight against stress, therefore having the power to combat disease.

So, did we cause our cancers by being stressed? Does relaxation help us recover? Are our families and friends the right therapy?

First, get over the guilt trip about having caused your sickness. This is a complex disease, with multiple factors. Having lived a perfect life would have been good, but that is really a silly thought, isn’t it? Second, stress isn’t good for much, so do all you can to reduce it. This study tells us that the best tonic is to set aside time for friends; keep connected with our families; talk to our neighbors; and just plain get out in the world.

Cancer survivors sought for thriving workshop

Stanford's Cancer Thriving and Surviving self-management online workshop is still looking for participants. It is open to adults over 19 who live in the U.S., have completed cancer treatment, and have access to the Internet. Here's how Stanford explains its program:

A 6 week, highly-interactive, online small-group workshop designed to give you ways to make your life less stressful and more rewarding, and to give you tools to take care of your health

15-25 people take the online workshop together

Workshop is facilitated by two trained moderators, one or both of whom also have survived cancer

Participation may be at 2-3 times during each week, for a total of 2 hours a week for 6 weeks

A study to evaluate the workshop's effectiveness

Blood Test Can Spot Breast Cancer

Researchers are refining a blood test that can identify breast cancer, differentiating between women with the disease and those without. The tests were on 121 women with suspicious mammograms, plus 6 women in a control group. Of these, 67 had cancerous tumors and 54 were non-malignant. The blood tests were effective in spotting the cancerous tumors, with a 79.5% accuracy, a sensitivity of 80.6% and a specificity of 78.3%.

The results were published in the journal Breast Cancer Research (January 2010). The researchers wrote:

[O]ur results indicate that gene expression in whole blood serves as a possible diagnostic tool for early detection of breast cancer. We have identified a gene signature that separates breast cancer patients from healthy women with good accuracy.

They say this is a supplement to mammography, not a replacement, although I have to ask why this can't ultimately replace those yearly doses of radiation.

This tool could constitute a fast and painless supplement to existing diagnostic technology, and offer a breast cancer test in areas where mammography screening is insufficient.

Brain Metastases More Common in TNBC Patients with Higher Stage Disease

Patients with later stage nonmetastatic triple receptor-negative breast tumors have a significantly increased early incidence of brain metastase, according to a retrospective study published in the Annals of Oncology. Researchers studied 679 patients with nonmetastatic triple receptor-negative breast cancer diagnosed from 1980 to 2006. Other factors—race, age, menopausal status, and grade of disease—were not significantly associated with the development of brain metastases. Of the 679:

• 145 (21.4%) were stage 1; 339 (49.9%) were stage 2; and 195 (28.7%) were stage 3.

• 87.3 percent had chemo either before or after surgery.

Median follow-up was 26.9 months. The results:

• 42 (6.2%) of the TNBC patients developed brain metastases —5.6% at 2 years and 9.6% at 5 years.

• 89.5 % of these had stage 3 disease.

• Median survival for all patients who developed brain metastases was 2.9 months.

• Median survival for patients who developed brain metastases as the first site of recurrence was 5.8 months.

Call me a Pollyanna, but I can’t help pointing out that this means that more than 90 percent of those studied DID NOT get brain metastases.

SOURCE: Dawood, S., Broglio, K., Esteva, F. J., Yang, W., Kau, S. . W., Islam, R., Albarracin, C., Yu, T. K., Green, M., Hortobagyi, G. N., and Gonzalez-Angulo, A. M. Survival among women with triple receptor-negative breast cancer and brain metastases. Annals of Oncology, 20(4):621-627.

Gefinitib No Benefit To Hormone Resistant BC

Gefinitib, which inhibits growth of the epidermal growth factor receptor (EGFR), showed no benefit to patients with advanced hormone-resistant breast tumors, according to a study in the Annals of Oncology. Patients included those with hormone-negative breast cancer and those with hormone-positive that had not responded to hormone therapy such as tamoxifen or an aromatase inhibitor. The latter is called hormone resistant, even though it is biologically hormone positive. Forty-five patients were given 500 mg of Gefinitib daily. Twenty-five were hormone-negative. At 24 weeks, enrollment was ceased because of low response. The conclusion: For these patients, tumors were not reduced and Gefinitib did not result in a clinical benefit rate (CBR).

SOURCE: Green, M. D., Francis, P. A., Gebski, V., Harvey, V., Karapetis, C., Chan, A., Snyder, R., Fong, A., Basser, R., Forbes, J. F., and Australian New Zealand Breast Cancer Trials Group (2009). Gefitinib treatment in hormone-resistant and hormone receptor-negative advanced breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 20(11):1813-1817.

Proteins Present in Aggressive Hormone-Negative Cancers

The tumors of especially aggressive forms of estrogen negative (ER-) breast cancer are more likely to contain cytokines than are less aggressive forms of breast cancer. Cytokines are small proteins that influence cells, causing them to act or inhibiting their function. They are released by the immune system. Specific types of cytokines, of IL-8, MCP-1 and MIP-1β, are especially important in the body’s defense against breast cancer.

Source: “Oestrogen receptor negative breast cancers exhibit high cytokine content,” Breast Cancer Research, January 2007.

Instead of a self-exam, try a healthy breast massage

Don't go looking for cancer. Cut toxins by taking care of your breasts.

One problem with breast self-exams might be in our reason for doing them—we’re looking for a lump that could mean we have cancer that could mean we are going to die. Soon. Wouldn’t it be better if we began taking care of our breasts using a life-affirming, non-threatening method that improves our connection to our bodies and allows us to notice changes along the way?

Sat Dharam Kaur, ND, offers such an option in her excellent book, The Complete Natural Medicine Guide to Breast Cancer. Kaur, director of The Healthy Breast Program in Toronto—you can order her book through them— says one key to avoiding cancer is to maintain proper circulation in our lymphatic system.

And we can do that through a breast massage, including the neck and armpits. This improves our lymph movement, Kaur says, and removes toxins from our bodies. Plus, we stop looking for lumps, which means we stop focusing on cancer. Instead, we focus on caring for ourselves.

Here’s how Kaur explains the process an excerpt from and article in New Living Magazine in 2004.

1) Place your hands on either side of your neck and gently move the skin back and down towards your collarbone. Do this 15 times. 2) Place the palm of your hand under your underarm and gently pump your armpit. The movement is slightly up toward your shoulder and in towards your body. Do this 15 times. 3) With soft hands, use the flat surface of three or four fingers to make small semi circles around the outer part of your breasts working inward until you reach the areola. Apply as much pressure as you would to stroke a young kitten. 4) With your hands cupped around your breast, gently pull your breast away from the chest wall and move your breasts in a circular or up and down movement. 5) If you do find a lump, have it checked out. Eighty percent of all breast lumps are benign, but it is important to bring any lump to your health care professional’s attention.

One Woman's View of TNBC

One of my readers says this is how she envisions a triple negative breast cancer cell might look.

When I was going through treatment, I read that I should visualize my cancer disappearing in white light. So, I would close my eyes and the vision of cancer that would come would be of a little black Pac Man-like character chomping its way through my cells.

Then I would envision the white light going after Mr. Man and he would disappear.

Pretty cool, really.

A Salad That Fights Breast Cancer

Adding pomegranates and nuts turns a simple salad of mixed greens into a dinnertime treat. Add a few crumbles of goat cheese and toss with a light vinaigrette dressing to keep down the calories. That’s all. Low cal, low fat, and full of cancer-fighting phytochemicals.

A study in Cancer Prevention Research, shows that pomegranates are especially good for estrogen-positive cancers, but even though they may not help those of us who have had cancers not responsive to estrogen (ER-negative, PR-negative, or TNBC), I am enjoying this treat anyway. I choose to avoid all types of cancer.

For more information on the pomegranate study, check out the news release from the American Association for Cancer Research:

Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.

Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate.

"Phytochemicals suppress estrogen production that prevents the proliferation of breast cancer cells and the growth of estrogen-responsive tumors," said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif.

Previous research has shown that pomegranate juice — punica granatum L — is high in antioxidant activity, which is generally attributed to the fruit's high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to estrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited.

Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth.

After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent estrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth. Read the entire release.

TNBC Goodies: Sweet Potato Fries

Here’s a fantastic recipe that fits the triple negative diet. My choice is Sandra Lee’s, from the Food Network. While they’re called fries, they’re actually oven-baked.

They’re low in fat and high in the antioxidant vitamin A, with a good amount of vitamin C, calcium and dietary fiber. All good foods to fight triple negative recurrence. However, they’re also high in sodium, so don’t overdo them.

And they are good—one of my new favorites. Yum times three.

For nutrition facts, check here.

Happy 2010!

A crummy economy, two wars, crazy people with explosives in their underwear--and, for many of us, a cancer diagnosis. It's time to say "so long" to the decade of the naughts. Still, it has been a good decade for me in many ways. I became a grandmother for the first time, and it's difficult to top that. Also, I was able to retire from my academic position and focus on my writing. I am 3.5 years post-diagnosis. My husband and I are fortunate to be healthy enough to hike at our Colorado cabin--and to have the cabin. And we have two great kids, a wonderful son-in-law, and that dear grandson.

I am optimistic about the coming decade for all of us. Researchers are spending more and more time looking for TNBC cures and treatment. And I am especially pleased to see so much research on health and fitness, on the at-home treatment we can control ourselves--diet and exercise, especially.

At the beginning of the decade, TNBC was barely recognized as a sub-group of cancer. Now, researchers are looking at subsets of TNBC. The Human Genome Project has opened up an understanding of the genetic definition of diseases, showing us that not all TNBC is created the same. Our unique DNA, they now say, creates a unique cancer.

I once wrote an article titled "The Wallflowers at the Breast Cancer Prom," in which I talked about how the research focus was on the "popular" cancer--hormone positive, ignoring those of us with hormone-negative. I no longer feel that way. I feel like we're out on the dance floor. And we're surviving long enough to get back to the tango of our lives. And, on especially good days, the salsa.

Ole!