The more we understand about our genes, the more we understand genetic diseases and eventually, how to best treat them.  The recent efforts of a nationwide consortium of researchers suggests that the origins of the type of breast cancer a patient is diagnosed with may inform the most effective course of treatment.

The study, published in Nature on September 23^rd, is one of the most comprehensive studies of breast cancer to date.  The study revealed that the gene expression profile for one of the most aggressive forms of breast cancer, basal-like carcinoma, is more similar with ovarian tumors than with other breast cancer subtypes.

The four main breast cancer subtypes: Luminal A, Luminal B, HER2, and basal-like, were confirmed and characterized by leading researchers at several institutions as part of The Cancer Genome Atlas Network.  The study is part of an NIH funded initiative with the Cancer Genome Atlas Network to build maps of genetic changes in common cancers.  While most historical studies of breast cancer have utilized one or two methods to analyze and characterize the gene profiles of breast cancers, six parallel technologies were used for this study to examine mutations and defects in DNA, RNA, and proteins.  Consortium scientists analyzed tumors from 507 women, with nearly 350 tumors being analyzed using all six technologies.

Basal-like breast tumors are also known as “triple negative” tumors.  Triple-negative tumors lack receptors for the hormones estrogen, progesterone, and human epidermal growth factor 2 (HER2), which are the gene targets of a number of approved chemotherapies such as Tamoxifen and Herceptin.  However, no receptor hormones means no drug targets.  Basal-like tumors are a considered high-grade, indicative of an abnormal appearance of the cells under a microscope and a tendency to grow and multiply more rapidly. These tumors have a poor prognosis for treatment and are more prevalent in younger women, women with BRCA1 and BRCA2 mutations, and women of African-American descent.

Currently, basal-like breast tumors are treated like most other breast cancers, using similar chemotherapy strategies.  However, basal-like breast tumors are aggressive and not been shown to respond well to therapies targeting hormone receptors or to standard chemotherapy regimens.  Consortium researchers found that each subtype could be identified by unique genetic markers, and that mutations in only three genes, TP53 (tumor suppressor gene 53), PIK3CA and GATA3, occurred in common with all four subtypes.  These findings suggest that not all breast tumors are alike and therefore, may not respond similarly to the same chemotherapy regimens.

Consortium scientists found that basal-like and HER2 tumor subtypes were characterized by the highest mutation rates.  Basal-like tumors shared common features with ovarian tumors and lung cancers, including high rates of TP53 mutations, BRCA1 inactivation, and a loss of RB1 and cyclin E genes, which are known to promote genome instability.  The study shows that 80% of basal-like tumors had TP53 mutations and approximately 20% also have mutations in the BRCA1 or BRCA2 genes. Mutations in the TP53 gene have been strongly linked to poor treatment outcomes, while BRCA1/2 mutations are known to increase breast and ovarian cancer.

A growing body of research suggests that tumors should be characterized and treated based on the presence of abnormal genes and abnormal gene expression profiles rather than on their location in the body.  Consistent with these findings, consortium researchers found that basal-like tumors are genetically more similar to ovarian tumors based on their genetic profiles.  Ovarian tumors are also characterized by a high frequency of TP53 mutations, widespread genomic instability and share other gene mutations in common with similar frequency.   These results give biologic reasoning to consider the potential benefits to patients with basal-like tumors to be treated with platinum-based chemotherapies currently approved for the treatment of ovarian cancer or PARP inhibitors which target tumors with BRCA1 and 2 defects.

Clinical trials are a lengthy but necessary step to determine if platinum-based compounds, currently used to treat cancers elsewhere in the body, and/or PARP inhibitors hold promise for patients diagnosed with basal-like breast carcinoma.  For now, this study offers much needed insight into the origins of the most aggressive form of breast tumor and promising possibilities for future personalized treatments.

A few days ago, we posted a blog about Giuliana Rancic’s personal experiences this year, first with infertility treatments, and then with a breast cancer diagnosis. Her story caused people to ask if her infertility treatments were related to her breast cancer diagnosis. Simultaneously, this fall, a scientific article was published that asked a similar question about any potential link between infertility treatments, such as in vitro fertilization (IVF), and breast cancer.

IVF is the process by which a woman’s eggs are combined with sperm in a laboratory setting to produce an embryo. For this procedure, a woman undergoes hormonal stimulation to cause the release of multiple eggs from her ovaries, which are then surgically retrieved. While some studies have previously found that there may be an increased risk for breast cancer in some patients who participate in infertility treatment, no cause-and-effect relationship has been identified. Dr. Jacqueline Jeruss and colleagues recently examined whether exposure to hormones during infertility treatment may cause the development of cancerous breast cells or affect the proliferation of cancer cells. They investigated this question with the use of breast cancer cell lines in a laboratory setting.

In the journal, Human Reproduction, the researchers communicated the effects of estrogen, progesterone and human chorionic gonadotropin (hCG), which are all hormones that are elevated during infertility treatment or early pregnancy, on breast cancer cell lines. In addition, they examined how these cells may be affected by clomiphen citrate, also known as Clomid, a drug frequently used to increase egg production in women prior to egg retrieval. The authors found that Clomid, progesterone, and hCG were all found to either have no effect on breast cancer cells or reduce their division and growth. As hCG is elevated in early pregnancy, this study raises the possibility that pregnancy may actually have protective effects on reducing breast cancer risk.

In the same article, “Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro,” one type of breast cancer cell line, derived from breast cancer cells that contain estrogen receptors (ER positive), responded to the estrogen treatment with increased cell division and growth. About 70% of breast cancers are ER positive, so women with a predisposition to these cancers, such as those with a BRCA2 mutation, may want to discuss breast cancer risks of infertility treatment with their doctors. However, women with mutations in the BRCA1 gene are more likely to have ER negative tumors, especially those who are diagnosed under age 40. In the study by Cooley et al., BRCA1 breast cancer cells responded to Clomid and progesterone with a decrease in cell division, indicating that BRCA1 women may not be at increased risk for breast cancer after infertility treatments. This information may help women who are at high risk for breast cancer to better understand their risk of breast cancer after infertility or oncofertility treatments.

According to the American Cancer Society (ACS), a woman in the United States is diagnosed with breast cancer every three minutes. This breaks down to a 12 percent, or 1 in 8, lifetime risk for women of developing breast cancer in the U.S. and right now, there are about two and a half million breast cancer survivors. Chances are, those of you who are reading this blog have been affected by breast cancer either personally or indirectly, through family and/or friends who have been diagnosed.

For those of you with questions about breast cancer treatment options, family history, diagnosis and support services, the Lynn Sage Breast Cancer Town Hall Meeting will take place on Sunday, October 2^nd at Northwestern University’s Chicago campus. It is an interactive discussion with Northwestern healthcare providers, providing you with an opportunity to have your questions answered by experts, learn about local and national support networks and meet with breast cancer advocacy groups.

Among the expert panel of healthcare providers will be our own, Kristin Smith, answering any questions you may have regarding fertility preservation and fertility options prior to and following cancer treatment. Joining Kristin will be a panel consisting of a cancer geneticist, radiation oncologist, survivorship and support expert, and a surgical oncologist. It’s a great venue to get more information and meet others, who may have gone through or are going through, a similar experience with breast cancer.

The town hall meeting is a free event and open to the public. There will be ample time provided for attendees to ask questions and get answers from our expert panel so come prepared with your most pressing concerns. For more information, including registration and directions, please visit www.cancer.northwestern.edu or call 312.695.1304. Walk-ins are always welcome so don’t let a little thing like registration hold you back! The most important thing is that you join us and get the answers and support you need.

Here at the Oncofertility Consortium Blog, it’s important to us that our readers who may be diagnosed with cancer or know someone that is, have a wealth of resources to tap into for support. A cancer diagnosis often leads to questions and concerns throughout the trajectory of the disease. Having organizations and support services readily available can be invaluable to a cancer patient.

One such resource is a long-standing organization founded in the late 70s, called SHARE (Self-Help for Women with Breast or Ovarian Cancer). SHARE’s mission is to create and sustain a supportive network and community of women affected by breast or ovarian cancer. SHARE brings women with breast or ovarian cancer and their support network of family and friends, together with survivors to provide participants with the opportunity to receive and exchange information, support, strength and hope. SHARE’s work focuses on empowerment, education and advocacy to bring about better health care, an improved quality of life, and a cure for cancer.

SHARE supports, educates, and empowers people affected by breast or ovarian cancer. The organization helps people face their feelings and fears, communicate effectively with their doctors, and make informed decisions about their health. All of SHARE’s services are free of charge, confidential, and provided by survivors. SHARE’s services include telephone support, educational programs, support groups, and public-health initiatives.

SHARE is managed by survivors helping people affected by breast or ovarian cancer and its support services and educational programs are provided in both English and Spanish. The organization also hosts Pink and Teal Seminars in which people learn about the risks, treatments, and early detection of breast and ovarian cancers from the unique perspective of survivors.

For a list of SHARE’s educational programs, including the support group, Young Women and Breast Cancer: Creating a Family After Cancer Treatment,  please click here. To learn more SHARE and the services they provide, please visit www.sharecancersupport.org.

Many Americans have heard of the term “interdisciplinary research” but don’t really understand how that affects them on a daily basis. Interdisciplinary research crosses traditional professional boundaries. Within science, it incorporates researchers from departments as different as physics, psychology, and biology. True interdisciplinary research also entails collaboration between larger fields that link researchers from the sciences, humanities, economists, and pretty much anything else you can think of.

More than 28% of biomedical research in the U.S. is funded by the National Institutes of Health (NIH). While you may not be familiar with the NIH, you have most certainly benefited from their research. The NIH funds most of the research done at hospitals and universities around the country, affecting many aspects of science, medicine, and the economy.

The NIH has a different perspective than the for-profit companies that perform biomedical research. In contrast to private industry, the NIH has long-term goals that allow it to support many facets of scientific research. Funding from the NIH pays for the training of young scientists, the development of medical technologies, and it is also interested in understanding basic science, such as the fundamental biology of human beings.

The basic science funded by the NIH often has no immediate clinical applications but, with time, it speeds medical advances. Just one example of basic science translating into medicine occurred in the cancer field. The first breast cancer genes, BRCA1 and BRCA2, were first identified with no immediate medical use. Twenty years later, the knowledge of these mutations allows women to monitor and prevent breast and ovarian cancer (more on this later). Interdisciplinary research, including genetics, surgery, and ethics were all involved in this advance.

The NIH recognizes the value of interdisciplinary research and encourages it through the grants that they fund. The Oncofertility Consortium is funded on one such grant, called a Roadmap Grant, that funds research to solve persistent medical problems through interdisciplinary research that could not be solved within any single field along. With this funding, scientists, historians, lawyers, and medical professionals are working to prevent fertility loss due to cancer treatment, implement that treatment to patients, and examine the financial and ethical aspects of such treatments.

As the economy is still in the forefront of many minds, it is important to note that the American Recovery and Reinvestment Act didn’t just put people to work building roads and bridges. Many scientists were employed through this act, as depicted in this variation of the American Recovery and Reinvestment Act sign (above).  With the help of the NIH, interdisciplinary research is building a strong infrastructure for America. That is a population of healthy and well-informed citizens, scientists, and medical professionals.

This past Monday, Sarah Halberstadt, the National Program Manager for the group Bright Pink came to visit us at the Oncofertility Consortium. Bright Pink is a not-for-profit organization that educates and supports young women who are at high-risk for breast and ovarian cancer. The members of Bright Pink include women with a family history of these cancers and those who have high-risk mutations of the BRCA breast and ovarian cancer genes. These women have many issues to deal with at a young age, including a greatly increased chance of developing cancer and fertility issues. Halberstadt stated that at Bright Pink, “We divide our programs into three areas: education, support, and providing a sense of community for women who are at high-risk.”

These women have many options and decisions to deal with, which is actually a good thing. “Especially with breast and ovarian cancer, we are so lucky that there are incredible surveillance programs, preventative drugs, and surgeries, if that is what you want to do,” Halberstadt said. One pre-emptive treatment that these women often consider is ovarian tissue cryopreservation. Ovarian tissue cryopreservation decreases a woman’s risk for ovarian cancer and may allow her to preserve her fertility. These high-risk women can turn to the FERTLINE for medical advice from a Patient Navigator and to Bright Pink for community support.

Bright Pink provides the Pinkpal One-On-One Peer Support Program, which Halberstadt describes as, “A matchmaking service without all the romance and fancy dates. Basically, It is a one-on-one peer support program that pairs a women who is looking for some support with one who has walked a mile in her shoes.” They also provide Breast Cancer 101 presentations to communities around the country and will be launching an online video of the information in September with the help of the Cancer Support Community.

They provide printed materials to physicians around the country to pass around to patients including two Little Bright Books. One is targeted to young women who are themselves at high-risk for breast and ovarian cancers. According to Halberstadt, “It is an A to Z guide on how to be proactive with your health as a young woman and how to know what your family history means about your risk.” The other book targets breast cancer fighters and survivors. It guides them through talking to family members about their risks, a process that is also therapeutic.

As the members of Bright Pink are mostly young women, they also like to relax through fun outreach events. As the organization grows, so will their programs. We look forward to hearing more about Bright Pink in the future!

In 1990, Mary-Claire King, PhD made a groundbreaking discovery: she identified a gene that was similar in people with inherited forms of breast cancer. She identified this gene by examining families with rare forms of breast cancer, such as those occurring early in life, in both breasts, or among male family members. The gene had very similar sequences, or mutations, among family members with breast cancer even though it is quite variable in the general population. Dr. King and others named this gene breast cancer 1, or BRCA1, and discovered that some mutations are associated with a greater than 60% lifetime risk of developing breast cancer.

Why are mutations in BRCA1 associated with cancer? The BRCA1 gene encodes a protein that repairs DNA when it is broken. When BRCA1 is mutated, damaged DNA is not repaired, potentially causing a cell to divide uncontrollably and become cancerous. Another related gene, called BRCA2, is also associated with increased breast cancer risk.

Interestingly, people with BRCA1 or BRCA2 mutations are also at greater risks of developing other cancers, especially ovarian cancer. Depending on the mutation, this risk can be as high as 55% over the course of a woman’s lifetime.

With the popularization of genetic testing over the last decade, people with the most severe BRCA mutations have taken a pro-active approach to cancer risk. These women have often seen family members die from cancer and consider mastectomies to preemptively stop any cancer in its tracks. Women may also opt for surgical ovarian removal, called oophorectomy, which causes infertility and thrusts them into menopause. As such, younger women often struggle with desires to have children and those to prevent cancer.

Current techniques in oncofertility, such as ovarian tissue cryopreservation (OTC), are not options for BRCA patients. OTC entails removal of the ovaries, cryoprotection and freezing, followed by reimplantation when a woman is ready to conceive a child. Unfortunately, ovarian implantation may also implant cancerous tissue into a BRCA patient and is not used for these women. Current research at the Oncofertility Consortium is working to develop new treatments for BRCA patients.

The FDA recently changed its stance on genetic testing that individuals can carry out in their own homes. People who want these genetics tests send DNA samples through “spit kits” to the laboratories that provide such services. The Food and Drug Administration (FDA) did not previously regulate in-home genetic testing because all samples are analyzed at company-owned laboratories. This contrasts with other medical diagnostic kits, which are evaluated in hospitals and laboratories around the country. Last week, the FDA sent out letters to in-home diagnostic companies requiring them to apply for approval or prove the clinical validity of their devices.

The FDA wants to regulate in-home tests because “Consumers may make medical decision in reliance on this information,” as stated in letters to multiple companies. For example, individuals who test positive for specific mutations of the BRCA1 or BRCA2 genes have increased risks of cancer.  Some mutations indicate that a person may have an 85% risk of breast cancer compared to the 13% risk in the general population. Individuals with BRCA gene mutations also can have a 54% risk of ovarian cancer, up from 2%. In response, people may elect preemptive mastectomies or ovarian removal to prevent such cancers, two surgeries that should not be taken lightly and rely on accurate information.

While in-home diagnostic tests may be attractive due to ease-of-use, patients enjoy the care provided from testing in a clinical setting. “At most hospitals, clinical geneticists are at hand,” says Kristin Smith, Patient Navigator for the Division of Fertility Preservation at Northwestern University. This allows a patient to learn their genetic results and receive comprehensive options in a “fast process,” says Smith. Whether genetic testing is done in-home or at a clinic, increasing the number of people who receive such personalized preventive medicine will decrease the number of cancer patients in future decades.