Tuesday, July 26, 2016

Cloudy Evidence on Skin Cancer Screening Shines Light on Prevention

The U.S. Preventive Services Task Force (USPSTF) reported today in the journal, JAMA, that there is not enough evidence to recommend that adults get screened for skin cancer. Though some professional medical organizations recommend physician-performed visual checks for skin cancer -- and many physicians carry them out -- the USPSTF found no solid evidence that "early detection of skin cancer through visual skin examination by a clinician reduces morbidity or mortality." Essentially, screening was not found to save lives.

On top of this, skin cancer screening itself is not without some risks. Though the Task Force concluded that was not enough evidence to fully explore the potential harms related to screening, it is likely to lead to unnecessary biopsies and other follow up tests as well as increased stress and worry in patients told they have a suspicious mole or other lesion.

On balance, the evidence was just too sparse and too ambiguous on potential harms and benefits for the Task Force to recommend skin cancer screening.

While research on screening continues to develops, these current conclusions point to the importance of also working to control skin cancer through a greater focus on prevention -- a point made in an accompanying editorial in JAMA Internal Medicine by Eleni Linos, Kenneth Katz, and CNiC's Graham Colditz. In addition to educating individuals about UV-safe behaviors (figure), policy approaches need to focus on areas such as limiting youth access to indoor tanning, promoting comprehensive campaigns that help change social norms related to tanning, and developing infrastructure that supports UV-safe behaviors, like shade structures and sunscreen dispensers.

Admittedly, it can be hard to believe that skin cancer screening has not been found to be a net health benefit.  It seems such a simple and common sense way to save lives.  Unfortunately, cancer is a very complex disease and not all screening exams have been proven to be effective tools to help prevent disease and lower mortality.  In fact, there are only a handful of cancers with recommended screening tests -- breast, colon, cervical, and lung cancer.

As the science develops, skin cancer may be added to that list, but right now efforts to combat skin cancer through prevention are key. As Linos and colleagues conclude: "we should...fully implement skin cancer primary prevention by eliminating indoor tanning exposure, especially among youths, and increasing the use of sun-protection strategies that work."

Tuesday, July 19, 2016

2nd Rural Cancer Disparities Partnership Retreat, July 15, 2016 (Photos)

Photos from Friday's very successful 2nd Rural Cancer Disparities Retreat at Washington University School of Medicine in collaboration with Southern Illinois University School of Medicine.

The P20 leadership team: from left: Sonya Izadi, WUSM project coordinator; Dr. Wiley Jenkins, SIU; Dr. Graham Colditz, WUSM; Dr. David Steward, SIU; Dr. Aimee James, WUSM; and Amanda Fogleman

Dr. Graham Colditz speaking on the goals of the Rural Cancer Disparities Partnership.

Dr. David Steward of SIU speaking on the cancer burden across Illinois.

Dr. David Steward of SIU speaking on the cancer burden across Illinois (con't).

Thursday, July 14, 2016

Genetic Risk of Breast Cancer and Your Options

Cancer News in Context is excited to publish four posts this week on high-risk breast and ovarian cancer.  These posts will provide insight for women (and their families) from Washington University School of Medicine physicians on unique aspects of high-risk disease -- from genetic testing and treatment to prevention and risk management.  
July 11 - Overview: High-Risk Breast Cancer - Prevention and Risk Management
July 12 - High-Risk Ovarian Cancer: Identifying, Preventing, and Managing Risk
July 13 - Treating and Managing Future Risk in Women with Hereditary Breast Cancer
July 14 - Genetic Risk of Breast Cancer and Your Options
--      --     --

Elizabeth B. Odom, MD 
Resident/Clinical Trainee, Division of Plastic & Reconstructive Surgery, Department of Surgery
Jennifer Yu, MD 
Resident, Division of Plastic & Reconstructive Surgery, Department of Surgery

Genes are the code that are passed down from ancestors that determine everything about us – hair color, eye color, body type, and every other characteristic that makes you an individual. These codes also determine our risk for certain types of cancer, and certain changes or mutations in the gene can change the risk of cancer developing over your lifetime. 

One gene that has been studied extensively is the BRCA gene mutation that has been linked to a high risk for breast cancer. Under one percent of women have this genetic mutation. The average chance of an American woman developing breast cancer in her lifetime is around 12 percent, and the risk of having cancer in both breasts is rare.(1) However, without treatment, women with the BRCA gene mutation have a lifetime risk of breast cancer development of over 50 percent with a higher likelihood of breast cancer occurring in both breasts.(2) 

There is no proven way to prevent breast cancer, but generally, exercise, healthy weight, a diet full of fruits and vegetables, and the avoidance of tobacco leads to lower rates of disease. Breastfeeding has also been found to be somewhat protective in the development of breast cancer. However, for all women, not just those genetically susceptible, breast cancer screening is key. All women should get an annual mammogram after the age of 45, then every 2 years after the age of 55 if no cancer has developed. Screening may start earlier if there is a history of early breast cancer in the patient’s family. 

Women with a strong family history of breast cancer in relatives before the age of 50, or those who have a male relative with breast cancer may be tested for the BRCA mutation through a blood test. They may also begin having mammograms as early as 25 years old. If the test is positive, due to the high risk for cancer, women are referred to a breast specialist to discuss their treatment options. 

In 2014, there was a study published that found women with the BRCA mutation who undergo removal of both breasts (bilateral mastectomy) at the time of breast cancer treatment had half the lifetime risk of dying from breast cancer than those who underwent removal of just the breast affected by cancer.(3) Furthermore, because of the increased risk, women such as actress Angelina Jolie, may choose to have both breasts removed to prevent the development of breast cancer. This has been shown to reduce the incidence of breast cancer significantly.(4) This decision is highly individual and options for continued screening or surgical intervention should be discussed thoroughly between the patient, family members, and the treating physician. 

However, preventative mastectomy is becoming an increasingly popular option, especially with the availability of breast reconstructive procedures using either your own tissue or implant devices. Women who elect to undergo a bilateral mastectomy to treat or prevent cancer are usually referred to a plastic surgeon to discuss the best reconstructive option for them. In many cases, the breasts may be reconstructed the same day as the mastectomy procedure. 

There is some increased risk of operative complications when having both breasts removed, however, after bilateral mastectomy and reconstruction, women no longer need to undergo annual mammogram screening, have less anxiety about the development of breast cancer, and are satisfied with the way their breasts look, particularly with clothing.(5) If you or someone you know is concerned about their risk of breast cancer, discuss this with your physician. There are well-known strategies of early detection and prevention, and the treatment options today are better than ever. 

1. Howlader N NA, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/ , based on November 2013 SEER data submission, posted to the SEER web site, April 2014. 
2. Levy-Lahad E, Friedman E. Cancer risks among BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2007;96(1):11-5. Epub 2007/01/11. doi: 10.1038/sj.bjc.6603535. PubMed PMID: 17213823; PMCID: PMC2360226. 
3. Metcalfe K, Gershman S, Ghadirian P, Lynch HT, Snyder C, Tung N, Kim-Sing C, Eisen A, Foulkes WD, Rosen B, Sun P, Narod SA. Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ. 2014;348:g226. Epub 2014/02/13. doi: 10.1136/bmj.g226. PubMed PMID: 24519767; PMCID: PMC3921438. 
4. Lostumbo L, Carbine N, Wallace J, Ezzo J. Prophylactic mastectomy for the prevention of breast cancer. The Cochrane database of systematic reviews. 2004(4):CD002748. Epub 2004/10/21. doi: 10.1002/14651858.CD002748.pub2. PubMed PMID: 15495033. 
5. Koslow S, Pharmer LA, Scott AM, Stempel M, Morrow M, Pusic AL, King TA. Long-term patient-reported satisfaction after contralateral prophylactic mastectomy and implant reconstruction. Annals of surgical oncology. 2013;20(11):3422-9. Epub 2013/05/31. doi: 10.1245/s10434-013-3026-2. PubMed PMID: 23720070.

Wednesday, July 13, 2016

Treating and Managing Future Risk in Women with Hereditary Breast Cancer

Cancer News in Context is excited to publish four posts this week on high-risk breast and ovarian cancer.  These posts will provide insight for women (and their families) from Washington University School of Medicine physicians on unique aspects of high-risk disease -- from genetic testing and treatment to prevention and risk management.  
July 11 - Overview: High-Risk Breast Cancer - Prevention and Risk Management
July 12 - High-Risk Ovarian Cancer: Identifying, Preventing, and Managing Risk
July 13 - Treating and Managing Future Risk in Women with Hereditary Breast Cancer
July 14 - Genetic Risk of Breast Cancer and Your Options
--      --     --

Cynthia Ma, MD
Associate Professor, Division of Hematology & Oncology, Department of Medicine, 

Washington University School of Medicine

Most women with breast cancer are without an inherited genetic mutation. However, about 10 percent of breast cancers are hereditary that can pass along in blood relatives. A number of genes, including BRCA1/2, TP53, PTEN, PALB2, STK11, CDH1 and others, could cause hereditary breast cancer. Among these, BRCA1/2 mutation is most common, representing about 20 percent of the hereditary cases. These genes are often tumor suppressor genes that normally protect cells from cancer formation, mutations of which lead to loss of tumor suppressor function. For example, BRCA1 or BRCA2 is important for the accurate repair of any damages occurring in the DNA, the genetic code in the cell, to prevent cancer formation. When BCRA1 or BRCA2 is mutated, cells accumulate damaged or mutated DNA, leading to cancer.

It is important to identify hereditary breast cancer as it increases the chance of developing a second breast cancer or other cancer types in the patient. Family members could be carriers of the same mutation that predispose them to breast and other cancers. For example, breast cancer patients who are BRCA1/2 mutation carriers have a much higher risk of developing a second breast cancer, exceeding 60 percent if the first cancer was diagnosed at a young age. In addition, BRCA1/2 mutation carriers are at a significantly increased risk of ovarian cancer (40 percent in BRCA1 and 15 percent in BRCA2 mutation carriers) and other cancers such as prostate and pancreatic cancer.

As hereditary breast cancer tend to occur at a young age, in other family members and high risk ethnic groups (such as Ashkenazi Jewish descents), a detailed personal and family cancer history is important. In addition, breast cancer diagnosed in male should raise the possibility of hereditary breast cancer. Since breast cancer in BRCA1 mutation carriers are often triple negative (negative for estrogen receptor, progesterone receptor, and HER2), any patients with triple negative breast cancer diagnosed at age 60 or younger should be evaluated for BRCA1/2 mutations.

Breast cancer patients who are BRCA1/2 mutation carriers are recommended to proceed with bilateral mastectomies rather than lumpectomy surgery when treating the initial breast cancer to reduce the risk of a second breast cancer and bilateral salpingo-oophorectomy to reduce ovarian cancer risk. This is often the preferred approach as it is highly effective, although some patients may elect with bilateral salpingo-oophorectomy alone which reduces the risk of ovarian cancer by at least 80 percent but also risks of breast cancer by about 50 percent when performed before menopause by reducing estrogen levels. Alternatively, hormonal therapy with either tamoxifen or aromatase inhibitors, which is often recommended to treat the breast cancer after surgery, could reduce the subsequent primary breast cancer diagnosis by 50 percent.

Other implications in the treatment of breast cancer in BRCA1/2 mutation carriers include the sensitivity of their breast cancers to platinum class chemotherapy and investigational Poly (ADP-ribose) polymerase (PARP) inhibitors. Although PARP inhibitors have not received food and drug administration (FDA) approval, pending large phase III studies, patients could potentially receive these drugs through participation in clinical trials.

In summary, effective prevention and treatment are available for breast cancer patients with inheritable mutations and their family members. All breast cancers, particularly if early onset, triple negative, in high risk ethnic group, in male, or with family history, should be evaluated for potential genetic causes of breast cancer. In addition to BRCA1/2, other genes could be in play. Genetic risk assessment is an integral part of cancer care for breast cancer patients.

Tuesday, July 12, 2016

Cancer Disparities in Rural America - 2nd Rural Cancer Disparities Partnership Retreat, July 15, 2016

by Katy Henke

For such an important issue, rural cancer disparities don't often get their due attention. Yet, it is understood by researchers and rural community members alike that geographic location has an important affect on population health and preventative health interventions. For individuals living in rural, isolated areas, a lack of access to healthcare can be a major burden in receiving appropriate care.

From 2010 Census data, roughly 19 percent of the American population lives in rural counties, with often vast distances between population centers and many health services (figure). Health research must focus on reducing health inequalities and cancer burdens experienced by many rural Americans.

Source: US Census Bureau, 2010

The National Institutes of Health (NIH) and the National Cancer Institute (NCI) have created multiple resources that are intended to help researchers address the needs of these isolated communities and help increase access to healthcare and cancer prevention screenings and prevention information. What can be done to reduce, and ideally eliminate, these disparities? Establishing relationships and collaborating with other organizations on rural cancer disparities research is crucial, as the NIH and NCI provides funds to continue this research to reduce cancer burden.

In 2013, Washington University School of Medicine and Siteman Cancer Center began working with Southern Illinois University School of Medicine to address rural cancer disparities in Southern Illinois from NIH grants. From this partnership, researchers from both institutions hope to reduce the burden felt by many residents and create appropriate, successful cancer intervention programs.

“Low-income rural communities experience significant cancer health disparities, including lower screening rates, increased incidence, later stage detection, poorer survival, and higher mortality rates. This is the unfortunate reality for much of the central rural, southern rural, and Delta (Downstate) regions in Illinois,” said Sonya Izadi, Senior Public Health Research Coordinator and Program Coordinator for the rural cancer disparities project at Washington University School of Medicine. “Together, we have created an integrated partnership to heighten awareness and build research capacity in addressing rural cancer disparities in Downstate Illinois. Ultimately, this partnership strives to narrow rural cancer disparities by reducing the cancer burden in the Downstate Illinois region.”

Providing access to healthcare is only one hurdle that rural communities face. Some community members may not have health insurance, may mistrust the healthcare system, or may not know that behavioral lifestyle changes can be one of the best ways to reduce cancer risk. Continued prevention campaigns and research are essential to overcoming these hurdles and helping reduce rural cancer disparities.

The Affordable Care Act has been instrumental in providing health insurance to low-income, underserved populations. Telephone health coaching campaigns have been successful at reaching isolated community members to provide health education, such as smoking cessation programs. Researchers are working towards finding solutions and implementing new cancer prevention techniques to help reduce rural cancer disparities and reduce the burden on community members. In order to keep pace with the growing population, research must continue to be funded to develop and implement appropriate solutions so rural communities receive the healthcare they deserve.

The 2nd Rural Cancer Disparities Partnership Retreat will be held on Friday, July 15th at the Washington University School of Medicine, offering the opportunity for investigators from Washington University, Siteman Cancer Center, and Southern Illinois University School of Medicine to learn about rural cancer disparities from people working in the rural central, southern, and Delta regions of Illinois.

High-Risk Ovarian Cancer: Identifying, Preventing, and Managing Risk

Cancer News in Context is excited to publish four posts this week on high-risk breast and ovarian cancer.  These posts will provide insight for women (and their families) from Washington University School of Medicine physicians on unique aspects of high-risk disease -- from genetic testing and treatment to prevention and risk management.  
July 11 - Overview: High-Risk Breast Cancer - Prevention and Risk Management
July 12 - High-Risk Ovarian Cancer: Identifying, Preventing, and Managing Risk
July 13 - Treating and Managing Future Risk in Women with Hereditary Breast Cancer
July 14 - Genetic Risk of Breast Cancer and Your Options
--      --     --

David Mutch, MD
Ira C. and Judith Gall Professor of Obstetrics and Gynecology, Division of Gynecology Oncology, Washington University School of Medicine

Cancer is a disease caused by a series of mutations in our DNA. This is true for ovarian cancer, the most lethal of all the gynecologic cancers. Like breast cancer, a predisposition of this disease can be inherited through inherited mutations in genes that are responsible for DNA repair. If one cannot repair DNA damage that occurs in the process of daily living then errors can accumulate in our DNA eventually leading to loss of normal cellular control. Known genes that are associated with inherited predisposition of ovarian cancer are the BRCA1 or BRCA2 genes and genes called mismatch repair genes (MLH1, MSH2, MSH6 or PMS2). These genes are all responsible for DNA repair so when they do not function properly DNA mutations accumulate in a more rapid manner than in a person without this defect.

Over five percent of the general population has a DNA abnormality that predisposes them to ovarian cancer. The lifetime risk of developing ovarian cancer if one inherits a mutation in one of these genes is over 50 percent. There is a great deal of data that suggests that if a woman has her ovaries removed in this setting, that one can nearly completely prevent ovarian cancer from developing. Oral contraceptives may also decrease the risk of developing ovarian cancer by 50 percent and therefore may be a good temporizing tool in young women. . The difficulty lies in determining who has a mutation in one of these genes and is therefore at high risk for developing ovarian cancer and will therefore benefit from intervention. Now that we can sequence an individuals DNA we can easily determine those at high risk but we need to know who to test.

Breast and ovarian cancer are linked and those who develop breast cancer are also at risk for ovarian cancer and visa versa. There are certain populations of individuals who are at high risk for having a mutation and can help us learn who should be counseled and tested.

Factors That Should be Considered When Considering Referring a Patient for Genetic Counseling for Risk Assessment of Familial Breast or Ovarian Cancer
  • Breast Cancer at younger than 40 
  • Family member with a male breast cancer 
  • Premenopausal breast cancer and a first- or second-degree relative with breast or ovarian cancer or two relatives of any degree or age 
  • Breast cancer or ovarian cancer in a family of Ashkenazi Jewish heritage 
  • High-grade papillary serous carcinoma of the ovary, fallopian tube or primary peritoneal cancer at any age 
  • Two primary cancers of the breast or breast and ovary at any age 
  • A known mutation within the family 
  • Bilateral breast cancer
Note: Peritoneal and fallopian tube cancers should be considered as part of the spectrum of the Hereditary Breast and Ovarian Cancer Syndrome. Close relative is defined as a first, second or third degree relative (ie mother, sister, daughter, aunt, niece, grandmother, granddaughter, first cousin, great grandmother, great aunt)

We believe that all people who are going to undergo testing should be counseled first and then undergo continuous counseling until they decide on treatment. Furthermore we believe that an affected individual within the family should be tested first. If there is a mutation then everyone who undergoes counseling and testing in that family can undergo testing for just that mutation. Furthermore, this is a dynamic situation, and we are now testing for many other genes than just BRCA1 or 2. Because of the development of new technology we can test many genes for the same or less cost than testing for a mutation in the BRCA genes a few years ago. These “panels” of genes are expanding and it is important for the genetic counselor to keep up with the patients so that they can be make aware of new developments.

Furthermore, formal hereditary cancer risk assessment should include review of at least a 3-generation pedigree, including first-degree, second-degree, and third-degree (cousins) relatives from both maternal and paternal families. Occasionally, expansion of the pedigree beyond these relatives may reveal important information that will guide recommendations for genetic testing and medical management.

The process of helping people understand and adapt to medical, psychological and familial implications of genetic contributions to disease. This process integrates the following: interpretation of family and medical histories to assess the chance of disease occurrence or recurrence; education about inheritance, testing, management, prevention, resources and research; counseling to promote informed choices and adaptation to the risk or condition.

Once risk has been determined then the patient can decide with the help of the health care professional how to proceed with the results. Prophylactic surgery, while the most effect preventive treatment may not be appropriate in young women who wish childbearing. The role of the genetic counselor and physician is to work together to develop the best treatment strategy for each patient and family member.