When Cancer Patients Should Ask For Genetic Sequencing

Cancer DNA can provide important clues about the best way to treat the disease, finds a new study published in the journal Nature Medicine. Doctors can genetically profile tumors by sequencing the DNA from a person’s cancer cells, revealing which mutations are responsible for causing the cancer. By comparing the tumor’s DNA to DNA from the same person’s healthy cells, the scientists can pinpoint which genetic changes were unique to the cancer cells.

In the new research, scientists at Memorial Sloan Kettering Cancer Center (MSKCC) sequenced more than 10,000 tumor biopsies and found that 37% of the people had at least one mutation that could be addressed, either with a prescription for an existing cancer drug or by taking part in a clinical trial testing new therapies. Other patients learned that they could take advantage of some of the newer immune-based therapies that are showing great promise. These findings are especially encouraging, says Michael Berger, associate director of the Center for Molecular Oncology at MSKCC, since the people in the study all had advanced cancer. That means they had tried traditional therapies that hadn’t worked and needed new options.

“What’s unique about our data set is that we collected samples from patients with advanced, metastatic cancer,” says Michael Berger, associate director of the Center for Molecular Oncology at MSKCC. “A lot of the other large-scale genomic databases look at untreated tumors [when patients are first diagnosed], and they provide a different genomic landscape and makeup than advanced cancers which are collected after several rounds of therapy.” Genetic testing is available at many major cancer centers, but it is still not a routine part of care for all cancer patients. And not all genetic tests look at so wide a swath of genes as the one used by MSKCC in the study, which analyzed more than 340 genetic changes. Another barrier is that not all insurance companies cover the cost of tumor sequencing, since they aren't yet convinced that it's a critical part of cancer care.

Berger and his colleagues hope that more data, like the kind provided by this study, will change that. For now, the technology is most useful for people with advanced cancers that have spread and those who have exhausted all of their treatment options. (For many people with early-stage cancers, existing therapies work well in controlling the disease.) Some hospitals offer commercial tests, but these often look at a limited number of cancer-related genes; the current study shows the value of doing a more comprehensive analysis. Doctors at MSKCC offer the test to people who might benefit from the genetic information, and it is either paid for by their insurance or covered by the hospital's philanthropic efforts, in most cases. The main advantage of the database, says Berger, is the fact that it is connected to patients who are currently receiving care at the hospital.

That means their tumor profiles are linked to the treatment options they chose and how well they did. This helps other doctors start to identify which treatment options lead to longer survival and better outcomes for people.That’s why the database is also being made available for free to any cancer doctor who is interested in learning from the information. Berger and his colleagues say that the database will only become more helpful for doctors treating patients, since the information will include how well they did on their various therapies.

Gene Tests Up Among Young Breast Cancer Patients

Amy Norton

A growing number of young women with breast cancer are being tested for the BRCA gene mutations that substantially raise the risks of breast and ovarian tumors, a new study shows.

Researchers found that of nearly 900 women who developed breast cancer at age 40 or younger, most had undergone BRCA testing within a year of their diagnosis.


And the percentage went up over time: By 2013, 95 percent had been tested, according to findings published online Feb. 11 in JAMA Oncology.

Experts called the results good news, since BRCA testing has long been recommended for women diagnosed with breast cancer before the age of 50.

"This is great, it's heartening," said Dr. Jeffrey Weitzel, director of clinical cancer genetics at City of Hope, in Duarte, Calif.

But, he added, women in the study were largely white, well-educated and had health insurance -- and it's unlikely that disadvantaged U.S. women would show the same high rate of BRCA testing.

"We need to keep working on extending the reach of genetic testing," said Weitzel, who co-wrote an editorial published with the study.

Media coverage following actress Angelina Jolie's disclosure that she carried the BRCA1 mutation has improved awareness about the testing and cancer preventive surgeries, previous research has suggested.

Jolie had both of her breasts removed in 2013 after learning she has the BRCA mutation. And, in 2015, she had her ovaries and fallopian tubes removed due to the significantly increased risk of ovarian cancer that stems from having the BRCA1 mutation. But, the authors of the new study note that the rise in gene testing among patients in this study largely predated Jolie's disclosure.

Inherited mutations in the BRCA1 and BRCA2 genes account for 5 to 10 percent of all breast cancers, and about 15 percent of all ovarian cancers, according to the U.S. National Cancer Institute.

Since the mutations raise the risk of early cancer, women who develop either disease at a young age have a relatively higher chance of harboring the flawed genes.

So BRCA testing is recommended for women diagnosed with breast cancer before age 50. That's, in part, to help guide their treatment decisions, explained Dr. Ann Partridge, the senior researcher on the new study, and an oncologist at Dana-Farber Cancer Institute, in Boston.

Women who carry the mutations have a high risk of developing a second cancer in the other breast, so some may want to opt for a double-mastectomy as a preventive measure. (Experts also advise women with BRCA mutations to have their ovaries removed by age 40, since there is no screening test for ovarian cancer, or any way to prevent it.)

BRCA testing also gives families information, Partridge explained. "On one hand, it could give them some peace of mind if the test is negative," she said. If it's positive, then certain family members may want to be tested, too, she added.

For the current study, Partridge and her colleagues surveyed 897 women who'd been diagnosed with breast cancer at age 40 or younger, at some point between 2006 and 2013. All were treated at one of 11 hospitals in Massachusetts, Colorado and Minnesota.

Of women diagnosed in 2006, 77 percent said they'd received BRCA testing. That went up to 95 percent among women diagnosed in 2013, the study reported.

Overall, about 12 percent of women who were tested had a BRCA mutation. And most of those women -- 86 percent -- decided to have a double-mastectomy, the study showed.

But half of the women who tested negative for a BRCA mutation also had a double-mastectomy, the researchers found.

That's concerning, both Partridge and Weitzel said. Women without the gene mutations have a low risk of developing a second cancer in the other breast, and there's no evidence that a double-mastectomy improves their long-term survival.

"We don't want to be doing procedures that aren't medically indicated," Partridge said.

It's not clear why so many women with negative test results opted for a double-mastectomy -- but it's also not surprising, Partridge noted, since it's consistent with past studies.

"Some women may do it for peace of mind," Partridge said, "or because they do believe it will improve their survival, even though there's no evidence."

At a time of high anxiety, she said, some women may not fully process the risk/benefit information they're hearing.

According to Weitzel, BRCA testing should ideally include genetic counseling, to help ensure that women understand their results.

But in reality, that counseling does not always happen, he said.

Under the Affordable Care Act, also known as Obamacare, BRCA testing is a covered preventive service for women at high risk of having a mutation. And, Weitzel said, Medicaid is now paying for testing, though the coverage varies by state.

There's still work to be done to improve "underserved" women's access to BRCA testing and counseling, Weitzel said -- including women in lower-income countries.

Study Shows Third Gene as Indicator for Breast Cancer

As appeared in the New York Times
By NICHOLAS BAKALAR

Mutations in a gene called PALB2 raise the risk of breast cancer in women by almost as much as mutations in BRCA1 and BRCA2, the infamous genes implicated in most inherited cases of the disease, a team of researchers reported Wednesday.

Previous data had indicated that mutations in PALB2 were linked to breast cancer, and many genetic tests already screen for them. But it had not been clear to what extent these mutations raised a carrier’s odds of developing the disease.

Dr. Marc Tischkowitz, an associate professor of medical genetics at the University of Cambridge, and his colleagues studied 362 members of 154 families with PALB2 mutations. None had BRCA1 or BRCA2 mutations, but all had at least one family member with breast cancer and a mutation in PALB2. There were 311 women with PALB2 mutations, of whom 229 had breast cancer, and 51 men with the mutation, of whom seven had the disease.

The results were published in The New England Journal of Medicine.

Over all, the researchers found, a PALB2 mutation carrier had a 35 percent chance of developing cancer by age 70. By comparison, women with BRCA1 mutations have a 50 percent to 70 percent chance of developing breast cancer by that age, and those with BRCA2 have a 40 percent to 60 percent chance.

The lifetime risk for breast cancer in the general population is about 12 percent.

The breast cancer risk for women younger than 40 with PALB2 mutation was eight to nine times as high as that of the general population. The risk was six to eight times as high among women 40 to 60 with these mutations, and five times as high among women older than 60.

The scientists were not able to explain why younger women with the mutations were at higher risk. And there were too few men, Dr. Tischkowitz said, to make a judgment about their risk.

The data also indicated that women with the PALB2 mutations were slightly more likely to have “triple negative” breast cancer — a form resistant to hormone treatment, more aggressive, and more likely to recur than other subtypes.

Dr. Anees B. Chagpar, the director of the breast center at Yale-New Haven Hospital, who was not involved in the work, said she was impressed with the study but cautioned that other factors must be considered in evaluating a woman’s risk.

“This has to be tailored to the patients, who may have other mutations and varying family risk,” she said. “With no family history, the increase they found is 35 percent. If you have two or more family members with cancer, they found a risk of 58 percent.”

The study used data from 14 sites in eight countries but found no significant geographic variations in its prevalence. The researchers write that larger studies are needed to detect such differences, as well as to assess the role of lifestyle and hormone use on breast cancer risk in PALB2 mutation carriers. Breast cancer risk depends not just on genes, but how they interact with the environment.

Official guidelines do not recommend screening for breast cancer genes in most women, only for those with a family history of the disease. Dr. Tischkowitz said that such women should consider testing for PALB2 mutations if they are negative for BRCA1 and BRCA2 mutations.

Dr. Chagpar said: “As the testing becomes more common, we’ll hopefully end up with studies with thousands of patients in them. We’re going to start getting answers to hard questions.”

Top Six Free Health Services for Women

Did you know the Affordable Care Act mandates that new insurance plans provide 19 free, preventive health services for women?

In the past, many health plans covered some or all of these services, but they often required cost-sharing (e.g., copays). Now -- as long as these services are administered by a provider in your network -- they are free of charge. They do not incur copays or coinsurance, and are free whether or not you've met your annual deductible.

The following is a list of the top 6 services that all women should have.

1. Breast cancer genetic test counseling (BRCA)
If you're a woman with a family history (e.g., two or more first-degree relatives) of breast cancer or ovarian cancer, you should ask a trained medical professional about whether to get genetic testing. If your provider recommends it, you will be tested for mutations in the BRCA gene and can be counseled on whether taking certain medications to lower your risk is right for you.

2. Breast cancer mammography screening
Women over 40 should start getting annual mammograms, and women over 50 should get mammograms every two years. Talk to your doctor to determine how often you, personally, should get a mammogram.

3. Breast cancer chemoprevention
Your provider can counsel you about medications to lower your breast cancer risk. Your plan will also cover you if you choose to go ahead with these cancer-prevention medications. There are currently two FDA-approved drugs -- tamoxifen and raloxifene -- that may lower your risk of breast cancer, if you have a significant family history of breast cancer or ovarian cancer.


4. Cervical cancer screening
Sexually active women should have regular cervical cancer screening tests every three to five years depending on your age and how often you get HPV tests. Cervical cancer deaths are preventable if women get regular Pap tests and abnormal cells are found before they turn into cancer. Pap tests should be administered every three years and can be provided during your well-woman visits.


5. Human papillomavirus DNA test
This can be done in concert with the cervical cancer screening during your Pap test, which in turn can be done during your well-woman visit. If you're not at high risk, you should be tested every three years once you turn 30. Speak your provider to determine how often you should be tested.


6. Well-woman visit
All women under 65 should have a well-woman visit every year. These visits provide age- and developmentally appropriate care, and often provide other preventive services as well.

Study ties breast gene to high-risk uterine cancer

BY MARILYNN MARCHIONE
AP Chief Medical Writer

Women with a faulty breast cancer gene might face a greater chance of rare but deadly uterine tumors despite having their ovaries removed to lower their main cancer risks, doctors are reporting.


A study of nearly 300 women with bad BRCA1 genes found four cases of aggressive uterine cancers years after they had preventive surgery to remove their ovaries. That rate is 26 times greater than expected.

"One can happen. Two all of a sudden raises eyebrows," and four is highly suspicious, said Dr. Noah Kauff of Memorial Sloan Kettering Cancer Center in New York.

His study, reported Monday at a cancer conference in Florida, is the first to make this link. Although it's not enough evidence to change practice now, doctors say women with these gene mutations should be told of the results and consider having their uterus removed along with their ovaries.

"It's important for women to have that information ... but I think it's too early to strongly recommend to patients that they undergo a hysterectomy" until more research confirms the finding, said Dr. Karen Lu, a specialist in women's cancers at MD Anderson Cancer Center in Houston.

She plans to study similar patients at her own hospital, the nation's largest cancer center, to see if they, too, have higher uterine cancer risks.

About 1 in 400 women in the U.S., and more of eastern European descent, have faulty BRCA1 or BRCA2 genes that greatly raise their risks for breast and ovarian cancer. Doctors advise them to be screened early and often for breast cancer, and to have their ovaries out as soon as they have finished having children to help prevent ovarian and breast cancer, because ovarian hormones affect breast cancer as well.

But the role of BRCA genes in uterine cancer isn't known, Kauff said.

His study looked at 1,200 women diagnosed with BRCA gene mutations since 1995 at Sloan Kettering. Doctors were able to track 525 of them for many years after they had surgery that removed their ovaries but left the uterus intact.

The vast majority of uterine cancers are low-risk types usually cured with surgery alone. Aggressive forms account for only 10 to 15 percent of cases but more than half of uterine cancer deaths.

Researchers were alarmed to see four of these cases among the 296 women with BRCA1 mutations. None were seen in women with BRCA2 mutations, Kauff said.

The study was discussed Monday at the Society of Gynecologic Oncology's annual meeting in Tampa, Fla.

Last year, the actress Angelina Jolie revealed she had preventive surgery to remove both breasts because of a BRCA1 mutation. Her mother had breast cancer and died of ovarian cancer, and her maternal grandmother also had ovarian cancer.

What you need to know about BRCA gene testing

What is BRCA gene testing?
Everyone has BRCA genes that produce tumor-suppressing proteins. But risky BRCA1 and BRCA2 gene mutations leave a person more susceptible to cancers, including breast and ovarian cancers. BRCA testing is used to determine whether a person has such a mutation, which can be inherited from either parent. Each child of a parent who has a mutation in one of these genes has a 50 percent chance of inheriting the mutation.

What does the test entail?
BRCA gene mutations are detectable through DNA from a blood or saliva sample. It usually takes about a month to get results once your sample is sent to a lab for analysis.

What does a positive result mean?
A woman's lifetime risk of developing cancer is “greatly increased,” if she has a harmful BRCA mutation, according to the National Institutes of Health. About 12 percent of women will develop breast cancer at some point compared with up to 65 percent of women who inherit a harmful BRCA1 mutation. Other cancers are linked to mutations in BRCA1 and BRCA2, including fallopian tube, abdominal and pancreatic cancers. Men with harmful BRCA gene mutations face higher risk of prostate cancer.

How common are high-risk BRCA gene mutations?
The likelihood of carrying a BRCA gene mutation is extremely low for people with no family history of breast or ovarian cancer. Only about 10 percent of all breast cancers and 15 percent of all ovarian cancers can be traced back to inherited genetic mutations.

Who should take the test?
Because BRCA gene mutations are relatively rare, many doctors agree only those who have specific family patterns of cancer should consider the test. Such patterns include having multiple family members who have been diagnosed with breast or ovarian cancer, especially at a young age; cases of male breast cancer; and two or more cancers in one family member.

For anyone thinking about such testing, experts strongly recommend genetic counseling by someone who is experienced in cancer genetics. Counseling can help assess the need for testing in the first place, as well as facilitate discussion about what kinds of decisions a person faces once she gets her results.

What kinds of decisions should you be prepared to make?
A person who finds out she has a BRCA gene mutation faces some difficult decisions. Some women choose enhanced cancer screening, beginning with regular mammograms in their 20s, for example. Others choose risk-reducing surgeries like mastectomies or the removal of the ovaries and fallopian tubes. People also consider chemo-prevention regimens of drugs and vitamins to delay or reduce cancer risk. Finding out you have a harmful BRCA mutation indicates a higher risk for your siblings, too, so what you learn can affect multiple family members.

How much does it cost?
Some insurance companies cover BRCA testing, which can range in cost from hundreds to thousands of dollars. The National Cancer Institute urges people to contact their insurance companies to discuss cost before getting the test. For those without insurance, some genetic testing companies offer free or discounted pricing for individuals who meet certain medical or financial eligibility standards.

Who can help?
There are myriad resources for people considering BRCA gene testing, including the Cancer Information Service at the National Institutes of Health (NIH) and many nonprofit organizations. Live and anonymous online chatting is available from the NIH weekdays from 8 a.m. to 11 p.m. ET (5 a.m. to 8 p.m. PT at http://livehelp.cancer.gov. You can also call 1-800-4-CANCER.