PALB2 Gene Mutation Affects Breast Cancer Risk

Having a family history of breast cancer nearly doubles a woman’s risk of developing the disease and genetic factors are known to play a major role in the origin of breast cancer.

The BRCA1 and BRCA2 genes were identified as major breast cancer susceptibility genes nearly 30 years ago and it is estimated that these gene mutations explain about 50 percent of familial breast cancer cases.  BRCA1 and BRCA2 mutation tests have been widely used in high risk women (e.g., women with a strong family history of breast cancer) for risk assessment and management which may include prophylactic surgical and drug therapy intervention.

However, a significant fraction of familial breast cancer cases remain unexplained. A recent study identified the PALB2 gene as another major breast cancer predisposition gene. The PALB2 (Partner and localizer of BRCA2) gene produces a protein that is crucial for key BRCA2 functions. Mutation carriers of this gene were found to have a 35 percent risk of developing breast cancer by the age of 70, triple the risk seen in the general population.  For breast cancer diagnosed before age 40, having PALB2 mutations was related to an 8 to 9-fold increased risk.  It is estimated the PALB2 mutations explain about 2 to 3 percent of familial breast cancer risk. This study expanded our knowledge of genetic contributions to the familial profile of breast cancer.

Currently, the benefit and risk of deploying preemptive measures like surgery or drug therapy based on PALB2 mutation status is unknown. While the utility of applying PALB2 mutation information for risk management of high risk populations needs to be further investigated, individuals with known mutations of this gene are encouraged to seek genetic counseling because PALB2 mutations are also known to increase the risk of pancreatic cancer and may increase the risk of ovarian cancers. Mutations in PALB2 are very rare in the general population. Thus, screening for PALB2 in the general population appears to be unnecessary.

Xiao Ou Shu, M.D., Ph.D., MPH
Ingram Professor of Cancer Research
Vanderbilt-Ingram Cancer Center

HPV-Positive Head and Neck Cancer Patients May be Safely Treated with Lower Radiation Dose

A new study suggests that lowering the dose of radiation therapy for some head and neck cancer patients may improve outcomes and cause fewer long-term side effects.

The research was presented by lead author Anthony Cmelak, M.D., professor of Radiation Oncology at Vanderbilt-Ingram Cancer Center (VICC), during the 50th annual meeting of the American Society of Clinical Oncology (ASCO), held recently in Chicago.

The study focused on patients with newly-diagnosed oropharyngeal cancers related to the human papilloma virus (HPV). More than two-thirds of new head and neck cancer patients have HPV-positive tumors and the number of these patients is on the rise. Cmelak’s prior cooperative group study found that patients with HPV-positive oropharyngeal cancer have significantly longer survival rates than patients whose tumors are HPV negative.

For the new study, 80 HPV-positive patients with stage III, or IVa,b squamous cell cancer of the oropharynx received induction chemotherapy, including paclitaxel, cisplatin and cetuximab.

After chemotherapy, 62 of the patients showed no sign of cancer and were assigned to receive a 25 percent lower dose of intensity-modulated radiation therapy – an advanced technology that targets the radiation beam more accurately to treat the tumor without harming surrounding tissue. The rest of the patients received a standard IMRT dose. The drug cetuximab was also given to both groups of patients along with the IMRT treatment.

Two years after treatment, the survival for the low-dose IMRT patients was 93 percent.  Those who did not have complete resolution of cancer following induction and went on to get full-dose radiation had an 87 percent two-year survival. Eighty percent of the low-dose patients and 65 percent of standard IMRT patients also showed no evidence of tumor recurrence.  Ninety-six percent of those who had minimal or no smoking history had no evidence of tumor recurrence after two years following treatment, and long-term side effects were minimal.

The investigators concluded that patients with HPV-positive cancer who had excellent responses to induction chemotherapy followed by a reduced dose IMRT and cetuximab experienced high rates of tumor control and very low side effects particularly for those with a minimal smoking history.

Treating tumors in the delicate head and neck region often causes side effects that can be troublesome and long-lasting, including difficulty swallowing, speech impairment, dry mouth, problems with taste and thyroid issues, so any therapy option that reduces these side effects can have an impact on patient quality of life.

“Treatment for head and neck cancer can be quite grueling, so it’s very encouraging to see we can safely dial back treatment for patients with less aggressive disease and an overall good prognosis, particularly for young patients who have many years to deal with long-term side effects,” said Cmelak.

He noted that lower-dose IMRT is not recommended for patients with HPV-negative cancer or larger tumors.

The authors note that further studies of reduced-dose IMRT in HPV-positive patients are warranted.

Other investigators include Jill Gilbert, M.D., VICC; Shuli Li, Ph.D., Dana Farber Cancer Institute, Boston, Massachusetts; Shanthi Marur, M.D., William Westra, M.D., Christine Chung, M.D., The Johns Hopkins University School of Medicine, Baltimore, Maryland;  Weiqiang Zhao, M.D., Ph.D., Maura Gillison, M.D., Ph.D., The Ohio State University, Columbus, Ohio; Julie Bauman, M.D., Robert Ferris, M.D., University of Pittsburgh Cancer Institute; Lynne Wagner, Ph.D., Feinberg School of Medicine, Northwestern University, Chicago, Illinois; David Trevarthen, M.D., Colorado Cancer Research Program, Denver;  A. Demetrios Colevas, M.D., Stanford University, California; Balkrishna Jahagirdar, M.D., HealthPartners and Regions Cancer Care Center, St. Paul, Minnesota;  Barbara Burtness, M.D., Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Funding was provided by The National Cancer Institute, a division of the National Institutes of Health (CDR0000665170).

 

Excerpt: Colon Cancer Screening Saves Lives

Widespread screening for colorectal cancer has helped prevent an estimated half-million cases of the disease since the mid- 1970s, a new study suggests.

At a time when screening for many kinds of cancer is being questioned, the findings underscore the importance of screening for colorectal cancer in saving lives, said the senior author of the study, Dr. James Yu, an assistant professor of therapeutic radiology at Yale School of Medicine.

Colonoscopies, beginning at age 50, are considered the gold standard in colon cancer screening, although other techniques, like fecal occult blood testing, can detect some cancers.

 To read the full article in The New York Times, please click here.

Today is National Cancer Prevention Day!

Everyday Ways to Prevent Cancer

By Leslie Vandever

February is National and World Cancer Month—observations meant to increase public awareness of cancer, cancer prevention, and cancer research. And Tuesday, Feb. 4 is National Cancer Prevention Day.

Even today, with the incredible scientific and medical advances that have taken place over the last hundred years, cancer remains one of the most frightening—and deadly—diseases we face. Fortunately, we’ve gotten much better at treating and even curing some types of cancer, some of the time. Unfortunately, a definitive cure for all cancers remains beyond our reach.

What is cancer?

Simply, “cancer” is the word for a group of diseases in which the cells—the body’s basic unit of life—develop abnormally and do not die when they should because of a mutation in their DNA. Instead, out of control, these “malignant” cells divide and spread (metastasize) to other parts of the body through the bloodstream or lymph system.

Sometimes mutated cells may form a mass of tissue called a tumor. It’s considered “benign” if it doesn’t spread to other parts of the body, can be removed, and doesn’t come back.

There are more than 100 different types of cancer. In many cases, what starts, or triggers, cells to mutate abnormally and spread is unknown. But scientists have been able to pinpoint some possible triggers for some forms of malignant cancer—and by avoiding or controlling those triggers, you can reduce your odds of contracting the disease.

What steps can you take toward cancer prevention?

  •  Don’t use tobacco. If you do, stop. Smoking has been linked to cancers of the lung, bladder and kidneys. Chewing tobacco has been linked to cancer of the oral cavity and pancreas.
  • Eat healthy. Choose a diet rich in plant-based foods like vegetables, fruit, beans, legumes and whole grains. Limit fat, particularly fat from animal sources. Avoid sugar. Foods that are higher in fat and sugar (and calories) contribute to obesity, which can cause cancer.
  • Avoid becoming overweight or obese. Maintaining a healthy weight for your age, height and build might help to prevent cancer. Obesity has been linked to cancer of the breast, prostate, lung, colon and kidney.
  • Exercise. Regular exercise helps to maintain overall health, helps to control your weight and might protect against breast and colon cancer.
  • Protect yourself from the sun. Many types of skin cancer are linked to the harmful ultraviolet rays in the sun. Use sunscreen liberally and wear tightly woven, loose-fitting clothes in bright or dark colors to protect exposed skin. Try to stay out of the sun between 10 a.m. and 4 p.m. And avoid tanning beds and sunlamps—they’re just as damaging as natural sunlight.
  • Cancer screening. Mammograms, PAP smears, breast and skin exams, and colorectal screening can catch precancerous conditions early. By finding abnormal cells and treating or removing them, some cancers can be prevented. They include cervical cancer, breast cancer and some skin cancers.
  • Chemoprevention.  The vaccine against the human papilloma virus (HPV) and the hepatitis B vaccine can prevent certain types of cancer. There are also medications can treat some pre-cancerous conditions and keep them from developing into a malignant form.

Other steps you can take include limiting the amount of alcohol you drink, and avoiding risky behavior. HPV and HIV infections, which can make you more susceptible to liver, cervical and other cancers, can be prevented by never sharing needles and practicing safe sex: limiting the number of sexual partners you have, and using condoms. Finally, visit your doctor at least once a year for preventive screening and an overall health checkup.

For more information about cancer and other health issues, click here.

Leslie Vandever is a professional journalist and freelance writer. Under the pen-name “Wren,” she also writes a blog about living well with rheumatoid arthritis called RheumaBlog (www.rheumablog.wordpress.com). In her spare time, Vandever enjoys cooking, reading and working on the Great American Novel.

References:

  •  What is Cancer? (2013, Feb. 8) National Cancer Institute. National Institutes of Health. Retrieved on January 26, 2014 from http://www.cancer.gov/

In honor of National Cancer Prevention Day, please consider making a donation to the T.J. Martell Foundation by clicking here. The Foundation funds cutting-edge research that will lead to clinical trials and drug discoveries that will help save lives!

 

Excerpt: Why Everyone Seems to Have Cancer

Every day in our work with cancer patients and research doctors, we are reminded of the importance of continuing to fund life-saving advancements and consistently renew our commitment to our foundation’s mission. A recent article in The New York Times states the eye-opening fact that cancer is about to overtake heart disease as the number one cause of death in this country, shining new light on the urgency of funding a cure:

Every New Year when the government publishes its Report to the Nation on the Status of Cancer, it is followed by a familiar lament. We are losing the war against cancer.

Half a century ago, the story goes, a person was far more likely to die from heart disease. Now cancer is on the verge of overtaking it as the No. 1 cause of death.

Troubling as this sounds, the comparison is unfair. Cancer is, by far, the harder problem — a condition deeply ingrained in the nature of evolution and multicellular life. Given that obstacle, cancer researchers are fighting and even winning smaller battles: reducing the death toll from childhood cancers and preventing — and sometimes curing — cancers that strike people in their prime. But when it comes to diseases of the elderly, there can be no decisive victory. This is, in the end, a zero-sum game.

 

The rhetoric about the war on cancer implies that with enough money and determination, science might reduce cancer mortality as dramatically as it has with other leading killers — one more notch in medicine’s belt. But what, then, would we die from? Heart disease and cancer are primarily diseases of aging. Fewer people succumbing to one means more people living long enough to die from the other.

The newest cancer report, which came out in mid-December, put the best possible face on things. If one accounts for the advancing age of the population — with the graying of the baby boomers, death itself is on the rise — cancer mortality has actually been decreasing bit by bit in recent decades. But the decline has been modest compared with other threats.

To read the full article, please click here.

Vanderbilt Researchers Find Potent Genetic Risk Factor for Breast Cancer

Researchers at Vanderbilt University have found a powerful new genetic risk factor for breast cancer.

Using data from population-based studies of women in Shanghai, China, Jirong Long, Ph.D., assistant professor of Medicine, and colleagues discovered a deletion in a cluster of genes, called APOBEC3 genes, that are known to trigger DNA mutation and which have previously been implicated in cancer.

If a woman has a deletion in one of the two sets of genes she inherits from her parents, her risk of breast cancer increases by 31 percent. If the deletion is present in both sets of genes, her risk increases by 76 percent.

“This is the first copy number variation or CNV identified for breast cancer and is one of the strongest common genetic risk variants identified so far for breast cancer,” the researchers reported in the Journal of the National Cancer Institute.

For the full article, please click here.

Martell Investigator Weighs in on H.I.V. Breakthrough

Doctors announced on Sunday that a baby had been cured of an H.I.V. infection for the first time, a startling development that could change how infected newborns are treated and sharply reduce the number of children living with the virus that causes AIDS.

The T.J. Martell Foundation is proud of our history of funding innovative HIV/AIDS research; Dr. Max Essex is our Principal Investigator and we reached him on site at the Botswana-Harvard AIDS Institute for comment.

“‘Cure’ and ‘eradication’ of HIV are words that were never used by AIDS researchers until very recently. But progress with powerful drugs has been very impressive in recent years. You will hear such terms used more and more.”

Dr. Essex is Chair of the Harvard AIDS Initiative (HAI), the Lasker Professor of Health Sciences at Harvard University, and Chair of the Botswana–Harvard AIDS Institute (BHP). He received his DVM degree at Michigan State University, his PhD at the University of California Davis, and was a postdoctoral fellow in the Department of Tumor Biology at the Karolinska Institute School of Medicine in Stockholm.

In 1982, Essex hypothesized, with Robert Gallo and Luc Montagnier, that a retrovirus was the cause of AIDS. For this the three shared the 1986 Lasker Award, the highest honor given for medical research in the U.S.

For more information about Dr. Essex’s AIDS research, please click here; for the full article, please click here.

Guest Blog Post – The Biologic Picture of Melanoma

Jeffrey A. Sosman, M.D., Director, Melanoma and Tumor Immunotherapy Program
Vanderbilt-Ingram Cancer Center

In the past 10 years, mutations found in melanoma (the most deadly form of skin cancer) have led directly to the development of effective therapies. One example is the BRAF mutation and its inhibitor drug vemurafenib.

The New York Times reported on a new finding uncovered in the DNA of a large number of melanomas tested with extensive DNA sequencing of the whole genome.  This new mutation found by two independent groups is actually not present in a gene that produces a functional protein or enzyme.  Instead, it is a mutation in the portion of the DNA that regulates the expression of an enzyme, telomerase. Telomerase protects the chromosomes from breakdown and the cell from death. High levels of telomerase are seen in many cancer cells, including melanoma, and it protects the cancer cells from a normal dying process.

In a mechanism previously never reported, the newly discovered mutation changes the regulatory portion of DNA so it may be very vulnerable towards activation. In this way, the mutation indirectly allows the telomerase level to increase.

This mutation is found in these exact locations in about 70 percent of melanomas. The mutation provides a link between the BRAF mutations and the regulatory portion of another gene.

The new discovery adds one more piece to the biologic puzzle of melanoma. With each additional piece we are closer to completing the biologic picture of melanoma, which will further our ability to define treatment approaches to kill this deadly cancer.

Give Yourself a Rewarding Experience

Singer/songwriter Colbie Callait, left, with CEO Laura Heatherly at the recent wine dinner in Beverly Hills.

This week I had the pleasure of attending the T.J. Martell Foundation’s Celebration of Wine Dinner in Los Angeles at Mr. C in Beverly Hills.

The evening was festive and brought together wonderful people associated in various areas of business: music, film, banking, travel, medical and real estate development.  Everyone had a special bond – they were lovers of food and wine and most importantly, they were there to help raise funds for the T. J. Martell Foundation’s pediatric cancer research programs at Children’s Hospital Los Angeles.

Foundation friend and supporter Wendy Dio of the Ronnie James Dio Stand Up and Shout Cancer Fund, left, with CEO Laura Heatherly, right, at the recent wine dinner in LA.

During the evening, I realized that the Foundation provides unique experiences from fun-filled events to having the opportunity to purchase celebrity or travel experiences in our auctions and to me, one of the most rewarding is meeting interesting people – some who actually become life-long friends.

Throughout the year, the T.J. Martell Foundation hosts numerous events around the country.  I encourage you to buy a ticket and attend one or more of our events and get to know our Foundation.  It can be rewarding in many ways and I hope you will enjoy it as much as I do.

For more photos from this terrific event, please visit the Gallery page of our website, tjmartell.org.