Breakthrough for eye melanoma

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For the first time, a systemic treatment has been found to be effective for a rare form of melanoma that affects the eye. This cancer is known as uveal melanoma, and it is one of the most challenging cancers to treat. Now comes an exciting report from the 2013 Annual Meeting of the American Society of Clinical Oncology pointing to a practice-changing development. A drug known as a MEK inhibitor appears to improve clinical outcomes for advanced disease. With the use of the drug Selumetinib, 50% of patients had some tumor shrinkage, and 15% had major tumor shrinkage. In the control arm (treatment with temozolomide), not a single patient had significant tumor shrinkage. The bottom line? This is the first study any systemic therapy has been shown to work among patients with ocular melanoma.

But… the drug will probably not be on the market for a couple of years. In this context, if you have advanced uveal melanoma, ask about clinical trials in which you might participate. I’m Dr. Michael Hunter

Addendum: MEK is a molecule that is activated by something called BRAF. When BRAF is mutated (changed) in melanoma, it directly activates MEK and unleashs a host of negative effects.

Gene flaws linked to black women’s greater breast cancer risk

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We have long known that African-American women who have breast cancer have a higher risk of death from the disease. Now, we have learned that gene flaws that raise the risk of breast cancer are surprisingly common among blacks who have the disease. A study reported today found that roughly 1 in 5 of these women have BRCA mutations, a problem we typically associate with women of Eastern European Jewish descent. These findings may help to explain why black women have higher rates of breast cancer at young ages, in addition to a higher risk of breast cancer-related death. Dr. Jane Churpek, the study leader, was very surprised by the results.

The study included 249 black breast cancer patients from the Chicago area. Many had breast cancer at a young age, and half had a family history of the disease. Here’s where the investigators went beyond the usual genetic testing: All patients had complete gene sequencing for all 18 known breast cancer risk genes rather than the usual tests that simply try to find a few specific mutations in BRCA genes. The results? Gene flaws were found in 56, or 22% of study participants; 46 involved BRCA1 or BRCA2, and the rest were less commonly mutated genes. Among black women with “triple negative” (estrogen receptor negative, progesterone receptor negative, HER2 negative), or the worst subtype of breast cancer, 30% had harmful mutations.

To me, the results point to the fact that too few African-American women have been included in genetic studies in the past. We really had no clue about the extent of mutations among this population. And if a parent has a BRCA mutation, children have a 50% chance of getting the gene. Today, we have more knowledge about the specifics of the gene problem among African American women with breast cancer. I’m Dr. Michael Hunter.

Physical activity after a breast cancer diagnosis

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I always counsel my patients about the role of physical activity in recovery. Almost inevitably, they are surprised that I ask them not to run a marathon, or work out for hours at the gym. In fact, I suggest doing what our grandparents did: WALK! So why do I focus on physical activity? Even light exercise may reduce the risk of death from breast cancer. In the Nurses’ Health Study, the greatest benefit occurred among women who did the equivalent of walking 3 to 5 hours per week at an average pace. In fact, there was little evidence of a link between increased benefit and greater energy expenditure. In addition, several studies have associated physical activity (after a breast cancer diagnosis) with improved quality of life. (http://jama.jamanetwork.com/article.aspx?articleid=200955#REF-JOC50040-4)

Physical activity can also reduce the risk of getting breast cancer. An expert panel of the International Agency for Research on Cancer of the World Health Organization estimated a 20% to 40% decrease in the risk of developing breast cancer among the most physically active women, regardless of menopausal status, type, or intensity of activity. (www.ncbi.nlm.nih.gov/pubmed/12119660) 

Physical activity has been linked to lower levels of circulating ovarian hormones, which may explain the association between physical activity and lower risk of breast cancer. Lower estrogen levels among physically active women with breast cancer could potentially improve survival, although we still need more data. However, irrespective of the amount of benefit in the breast cancer arena, why would you not want to lower your risk of other cancers, heart attack, stroke, diabetes, and maybe even dementia?

Erlotinib targeted therapy approved for metastatic lung cancer

Metastatic lung cancer is cancer that originated in the lungs and has spread to distant organs. It tends to go wherever the blood goes, including the liver, the bones, elsewhere in the lungs, and the brain. It is, alas, not curable. Still, chemotherapy and targeted therapies offer the possibility of improved quality of life, and can lengthen life as well. Hot off the press is news that the US FDA has approved a targeted therapy (erlotinib, also known as Tarceva) for the treatment of patients whose cancers have spread and who in addition have tumors that have something known as an epidermal growth factor receptor EGFR) mutation. Let’s take a closer look at this fascinating EGFR protein. There is a family of glycoproteins that poke out of the cell surface like antennae. We call them HER1, HER2, HER3, and HER4. In some patients with lung cancer, the HER1 is over expressed; there are too many of them. When the growth signal hits the EGFR receptor, it causes it to join arms with other HER family members, fueling the growth of the cell. Erlotinib (a pill) targets the EGFR.

On May 14, 2013, the US Food and Drug Administration (FDA) approved the use of a drug that targets the EGFR receptor. Here’s why the FDA took the step: A randomized, multicenter trial compared erlotinib (86 patients) to the more commonly used combination of a platinum chemotherapy drug with another drug (we call this a platinum doublet). All patients had to have an EGFR mutation.

The majority of the patients were female (72%), Caucasian (99%), never-smokers (69%), and had adenocarcinoma histology (93%). The median progression free survival (half of patients had progression by this point, half did not) was 5.2 months in the platinum doublet chemotherapy arm, and 10.4 months in the erlotinib arm. And the survival was a bit better with erlotinib, too: 22.9 months versus 19.5 months. The majority of the patients in the platinum-based chemotherapy arm (82%) subsequently received an EGFR tyrosine kinase inhibitor following investigator-determined disease progression.

What’s the downside of erlotinib? The most frequent (greater than or equal to 30%) adverse reactions of any grade in the erlotinib arm were rash, diarrhea, asthenia, cough, dyspnea and decreased appetite. The most frequent (greater than or equal to 5%) grade 3-4 (bad) adverse reactions in the erlotinib arm were rash and diarrhea. The recommended daily dose of erlotinib for NSCLC is 150 mg taken orally at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity.

Thank you for visiting. I’m Dr. Michael Hunter.

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Coming later this month: Understand Lung Cancer in 60 Minutes, an e-book for IPad.

Lung Cancer Radiation Therapy: Less is More

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Radiotherapy at a higher-than-standard dose is harmful to patients with locally advanced non-small cell lung cancer (NSCLC) who are also getting concurrent and consolidation chemotherapy, a study has found. Patients with stage III NSCLC who were given the standard 60 gray (Gy) dose of radiotherapy lived approximately nine months longer and experienced fewer treatment-related deaths than those treated with a high dose of 74 Gy. Those who received the high dose faced a 56% greater risk of death and a 37% greater risk of local progression of their disease compared with patients who received the standard dose, according to lead author Jeffrey D. Bradley, MD. This is a critical study in the field of radiation oncology,” said ASCO President Sandra M. Swain, MD. After a decade of research, we can finally close the chapter on the high-dose vs standard-dose therapy debate in lung cancer, You now have evidence that standard doses of radiation therapy for stage III non-small cell lung cancer are the gold standard for treatment. For more information on lung cancer, look for my new e-book for IPad (Understanding Lung Cancer in 60 Minutes) coming out this month. I’m Dr. Michael Hunter.