TNBC: The Statistics of Survival

The people whose discussions fill the Breastcancer.org forums are savvy folks. They are highly informed about the details of breast cancer—they read the research and discuss it like pros. So, when they came across an essay in The New York Times that presented some frightening statistics, they questioned it.

The piece, “Finding Little Comfort in the Statistics of Survival,”was written by Ellen D. Feld, M.D., an internist and teacher at Drexel University. Feld was diagnosed with a 2.2-centimeter tumor with no affected lymph nodes, making hers a stage IIA cancer. Her chances of survival, she writes, referring to an unnamed book, are at 70 percent for five years and 50 percent at ten years.

The writers on the BCO discussion boards, though, wanted to know where Feld got those numbers, as they are odds with their own research. Clarify and verify, they said.

“I notice the author doesn't quote a source for the numbers,” wrote Michelleo13.

“There is something we don't understand about those statistics,” wrote Mitymuffin.

This discussion thread was for women with triple-negative breast cancer and many of the writers also noted that Feld’s numbers don’t necessarily match the stats for TNBC. And nowhere in the article does she say what type of breast cancer she had—an omission that makes significant difference, as the statistics can vary a great deal from cancer to cancer, and TNBC women have much better long-term survival rates once they hit three years past diagnosis.

I appreciate Feld’s position of constantly worrying. We do that. In fact, I have written about it myself.

But why make others worry more? This is the unintentional result of Feld’s piece, which is otherwise well written. Wouldn’t it be better to advance the dialogue of hope rather than of terror?

So, let’s clarify and verify survival rates for TNBC.

In a study at the M.D. Anderson Cancer Center and published in the Journal of the National Cancer Institute (2008) of 2,838 women treated between 1985 and 2001:

• 93 percent of women with hormone-negative breast cancer had no recurrences within 5 years

• 89 percent had no recurrences after 10 years.

• They did not break other figures down by hormone receptor status, so these figures apply for all breast cancers: Within five years, those with stage I cancer had a 7 percent risk of recurrence; stage II faced an 11 percent risk; and stage III faced a 13 percent risk. Nowhere is there a 50 percent risk.

And in research on 1,601 patients with breast cancer diagnosed between 1987 and 1997 and published in Clinical Cancer Research (2007) at Women’s College Hospital in Toronto:

• The death rate for those ten years after diagnosis was zero. Nothing. Nada. No deaths.

• Most deaths were within one to three years of diagnosis.

I do not know where Feld’s numbers come from, but using these numbers as our guide, we can say estimate that, if her stage IIa tumor were triple-negative, she would face an 11 percent risk of recurrence within five years, a 0-11 percent risk within 10 years.

Remember that these are averages and are a bit like weather reports. When the forecaster says we face a 10 percent chance of rain on any given day, that means that, because of the specific weather conditions, there is a 1 in 10 chance it will rain. It seldom rains on those days. And we all can remember instances when the forecast told us a huge storm was coming and we ended up with sunny skies.

For more information on triple-negative breast cancer, check out my book, Surviving Triple-Negative Breast Cancer.  You can get a free signed copy just by donating $25 to this site.  Click the Donate button on the right to donate through PayPal.   You'll then get an email from me asking how you want your book signed and where you want it sent.  Thanks!  And hugs.

SOURCES:

Brewster, A. M. , Hortobagyi, G. N. , Broglio, K. R. ,Shu-Wan Kau, Santa-Maria, C.A. . Arun, B., Buzdar, A.U., Booser, D.J., Valero,V., Bondy, M., Esteva, F.J., “Residual Risk of Breast Cancer Recurrence 5 Years After Adjuvant Therapy.” Journal of the National Cancer Institute, 100(16):1179-1183. 2008.

Dent, Rebecca, Trudeau, Maureen, Pritchard, Kathleen I., Hanna, Wedad M., Kahn, Harriet K., Sawka, Carol A., Lickley, Lavina A., Rawlinson, Ellen, Sun, Ping Narod, Steven A., “Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence”, Clinical Cancer Research, vol. 13, no. 15, 4429-4434 (2007).

Should women with TNBC take vitamins and supplements?

After much research, I stopped taking a multivitamin several years ago. I had been inconsistent in using them in the past, but I had thought that my cancer diagnosis meant I needed more oomph in my diet. What I ultimately determined was that I did need a strong diet—but that meant eating healthy foods, not popping pills.

It is easy to turn to vitamins and supplements after a diagnosis—we need to do something proactive because, clearly, our bodies are not working right. But, what research has shown me is the multivitamins, in general, give you too many nutrients you don’t need and, as a recent study has shown, are associated with an increased risk of death in postmenopausal women.

The studies did not say multivitamins caused death, only that they were associated with an increased risk. It could be that women who took them were more at risk to begin with, or they opted for pills rather than an improved diet.

So, where does this leave us?

• Look at the labels of the foods you regularly eat to see what vitamins have been added there. Food companies often add B vitamins, folic acid, iron, and other nutrients to everything from breakfast cereal to canned soup. These additions may take care of your necessary dietary intake of these nutrients. And, if you eat these foods plus take a supplement, you could be overdosing.

• Diana Dyer, MS, RD, suggests you “read, read, read” to educate yourself on the use of supplements. I agree, and make food labels part of your reading lists.

• Some docs say antioxidants can interfere with the effects of chemo. Not so, say researchers, in an overview of 50 studies published in Alternative Therapies in Health and Medicine. They can actually make chemo more effective.

• Organic and natural foods often do not have added nutrients—only the vitamins and minerals that come naturally in the food itself. I tend to eat a lot of organic, so I do not get added doses in prepared foods.

• Vitamin D deficiencies have been linked to an increased risk of breast cancer, especially TNBC. But you can overdo it, and taking too much of the vitamin could possibly increase your risk of skin cancer. Go outside and get your vitamin D from the sun when possible—no sunscreen for 20 minutes or so. Researchers don't agree on an appropriate dose of vitamin D—although they agree it should be D3—doses do seem to be increasing. I take 4,000 daily units a day when I cannot get enough sun.

• Folic acid has been associated with a reduced risk of TNBC, and has been shown to counter the effects of alcohol.

• Calcium is important, especially for post-menopausal women. Try to get it through dairy, if you can tolerate it.

• Fish oil, or Omega 3s, help your body fight a multitude of ills. The safety of fish can be confusing—does it have mercury or other toxins?—so this might be a case in which the supplement itself makes sense.

• Check out the Triple-Negative Breast Cancer Diet for more details.

• The National Institutes of Health offer information on vitamins and herbs and supplements.

Topoisomerase 1 inhibitor for metastatic TNBC?

In a Phase 2 clinical trial, NKTR-102, a novel topoisomerase I inhibitor, showed promising results for women with metastatic triple-negative breast cancer, including patients previously treated with anthracycline/taxane/capecitabine. Both 2-week and 3- week regimens were effective. The news release from the drug's producer, Nektar Therapeutics, is below.

The major toxic effect of the drug--at least so far--is diarrhea. According the Nektar, "NKTR-102 exhibited minimal alopecia, neuropathy and neutropenia."

SAN FRANCISCO, Sept. 9, 2011 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) announced today that positive results from the company's Phase 2 clinical study of NKTR-102 in patients with metastatic breast cancer were presented at the ASCO 2011 Breast Cancer Symposium in San Francisco, California. NKTR-102 is a novel topoisomerase I inhibitor designed using Nektar's proprietary polymer conjugate technology, and is being developed in multiple tumor settings.

"NKTR-102 exhibits a very high response rate and excellent clinical benefit rate in patients with metastatic breast cancer, and importantly, this anti-tumor activity is maintained in each of the poor prognosis subsets within the study," said presenter and NKTR-102 study investigator, Dr. Agustin Garcia, Associate Professor of Clinical Medicine at USC Norris Comprehensive Center. "The data from the Phase 2 study also shows highly promising PFS of 5.3 months and OS of 13.1 months in the every three week dose schedule, which was also very well-tolerated. As a novel topoisomerase I inhibitor in breast cancer, NKTR-102 holds great therapeutic potential and allows us to address the challenge of resistance in this setting. The investigators look forward to the initiation of the Phase 3 BEACON study of NKTR-102 in patients with metastatic breast cancer."

More than one million women worldwide are diagnosed with breast cancer every year and the disease is the leading cause of cancer-related death among women.(1)

Highlights from the Phase 2 Clinical Data Presentation

The randomized Simon two-stage study of single-agent NKTR-102 evaluated two 145 mg/m2 dose schedules of NKTR-102, every two weeks (q14d) and every three weeks (q21d), in 70 metastatic breast cancer patients. NKTR-102 achieved a confirmed objective response rate by RECIST of 29 percent. In addition, 71 percent of patients in the study had no tumor progression, defined as complete response (CR), partial response (PR) and stable disease (SD), as measured by RECIST criteria. NKTR-102 also demonstrated a high clinical benefit (CR+PR+SD greater than six months) rate of 46 percent (30 of 66). Six patients experienced 100 percent resolution of all target lesions, with two complete RECIST responses and four near-complete responses. Objective tumor responses were maintained in heavily pretreated and poor prognosis subsets, including patients previously treated with anthracycline/taxane/capecitabine, patients with metastatic triple-negative breast cancer and patients with visceral disease.

NKTR-102 exhibited minimal alopecia, neuropathy and neutropenia, which are significant adverse events associated with existing and recently-approved breast cancer therapies. Side effects were generally manageable; most common Grade 3 toxicity was diarrhea (17-23%) typically occurring after three months of therapy for both schedules.

Eighty-nine percent (62/70) of patients in the study received a prior anthracycline/taxane with or without capecitabine. A total of 66 of the 70 patients treated with single-agent NKTR-102 in the Phase 2 clinical study were assessable for the primary endpoint of objective tumor response rate (ORR).

The slide presentation from today's oral session at the ASCO 2011 Breast Cancer Symposium is available on Nektar's website at http://www.nektar.com/product_pipeline/oncology_nktr-102.html.

BEACON Study Design

The company also announced today the design of the planned Phase 3 clinical trial of NKTR-102 in metastatic breast cancer patients. The BEACON study (BrEAst Cancer Outcomes with NKTR-102) plans to enroll approximately 840 metastatic breast cancer patients who have had prior treatment with anthracycline, taxane and capecitabine in either the adjuvant or metastatic setting. Patients will be randomized on a 1:1 basis to receive single-agent NKTR-102 once every three weeks or a single agent of physician's choice. The primary endpoint of the study will be overall survival, and secondary endpoints will include progression-free survival and objective tumor response rates. The global BEACON study, which will include over 130 investigator sites, is expected to begin in December 2011.

About Metastatic Breast Cancer

More than one million women worldwide are diagnosed with breast cancer globally every year(1). The chance of developing invasive breast cancer at some time in a woman's life is a little less than one in eight (12%). There are approximately 200,000 new cases of breast cancer in the United States and 430,000 in Europe each year.(2) Metastatic breast cancer refers to cancer that has spread from the breast to distant sites in the body.

Anthracyclines and taxanes (AT) are the most active and widely used chemotherapeutic agents for breast cancer, but the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Drugs used to treat patients who progress following AT treatment can have response rates as high as 20-30%; however, resistance develops rapidly and new agents with different mechanisms of action, such as topoisomerase I inhibitors, are needed to allow novel ways to overcome the problem of drug resistance.(3) There are currently no FDA-approved topoisomerase I inhibitors to treat breast cancer.

About NKTR-102

NKTR-102 is a next generation topoisomerase I inhibitor with a unique pharmacokinetic profile that provides a continuous exposure to active drug with reduced peak concentrations. NKTR-102 is a new chemical entity designed by Nektar using its polymer conjugate technology platform. NKTR-102 has been evaluated in two separate Phase 2 studies for the treatment of platinum-refractory/resistant ovarian cancer and metastatic breast cancer patients. In addition, NKTR-102 is also being tested as a single agent in a Phase 2 clinical trial in patients with second-line colorectal cancer and a Phase 1 clinical trial evaluating NKTR-102 in combination with 5-FU therapy.

About Nektar

Nektar Therapeutics is a biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugation technology platforms. Nektar has a robust R&D pipeline of potentially high-value therapeutics in oncology, pain and other areas. In the area of pain, Nektar has an exclusive worldwide license agreement with AstraZeneca for NKTR-118, an investigational drug candidate, being evaluated in Phase 3 clinical studies as a once-daily, oral tablet for the treatment of opioid-induced constipation. The agreement also includes NKTR-119, an earlier stage development program that is a co-formulation of NKTR-118 and an opioid. NKTR-181, a novel mu-opioid analgesic molecule, is being evaluated in Phase 1 clinical studies. In oncology, NKTR-102, a novel topoisomerase I-inhibitor, is being evaluated in Phase 2 clinical studies for the treatment of breast, ovarian and colorectal cancers.

SPARC may help define treatment for TBNC subsets

TNBC is not one disease, but many, with varying degrees of aggressiveness. New research may help doctors determine which subsets are the most aggressive, and how to treat them.

Secreted protein acid rich in cysteine (SPARC) is an important element in tumor development and can help determine the prognosis of patients with triple-negative breast cancer, according to a paper presented at the American Society of Clinical Oncology's symposium in September. Specifically, researchers noted that paclitaxel can be especially effective in cases in which SPARC overexpresses:

Our study suggests that nab-paclitaxel may serve as a therapeutic agent for the subset of triple negative patients that over-express SPARC. To the best of our knowledge, this is the first study involving a large patient pool in which SPARC has been investigated in a single clinical laboratory using standardized IHC with two different SPARC antibodies.

Will DNA repair yield new TNBC treatments?

Drugs that repair the DNA of cancer cells may lead to new treatments for TNBC, especially metastatic forms of the disease, although recent research has been disappointing. Here's a perspective from one of the researchers in that field, Joyce O’Shaughnessy, MD, of the Baylor Sammons Cancer Center in Dallas, who has studied the effects of gemcitabine and carboplatin on metastatic breast cancer. She spole at the American Society of Clinical Oncology's Breast Cancer Symposium in San Francisco in September. Her comments are in a Conference Report from the Cancer Network.

Partial-breast irradiation works for TNBC in Michigan test

Partial-breast irradiation—terstitial brachytherapy, balloon-based brachytherapy, or 3-dimensional conformal radiation therapy—proved effective in treating early-stage triple-negative breast cancer in research at the Beaumont Cancer Institute in Royal Oak, Michigan. Researchers followed 516 patients whose median age was 66 years for 4.9 years. Medscape has the story. Results were presented at the American Society of Clinical Oncology's 2011 Breast Cancer Symposium.

Researchers Target Inflammatory Response in TNBC

Researchers from the University of California at San Francisco have had promising initial results on studies using a drug targeting an inflammatory response that help fuels triple negative breast cancer, using a $6.5 million grant from Susan G. Komen for the Cure. Tests so far have been on mice, but researchers plan to do additional animal research and ultimately move to human subjects. Scientists on the project are Lisa Coussens, PhD, UCSF oncologist Hope Rugo, MD, and Shelley Hwang, MD, a surgical oncologist at Duke University. Read more here from UCSF.

Using the Internet Effectively for Health News

Andrew Schorr learned how to successfully navigate the Internet for information on chronic lymphocytic leukemia when he was diagnosed in 1996. He's written a book with Mary Adam Thomas, The Web-Savvy Patient, to help others get the most out of the web surfing—and avoid getting mired in misinformation and bad news. Here's The New York Times' review of the book.