Medical Device Daily Contributing Writer

SAN DIEGO — If ever there were to be a model of personalized medicine, it would be found in the domain of the American Society of Breast Surgeons (ASBS; Columbia, Maryland) and showcased at their annual meeting which was held here late last month.

The ASBS has more than 2,700 members and each year more than 1,000 of them attend their annual meeting – the only medical meeting dedicated exclusively to the latest issues affecting surgeons who treat breast disease from diagnosis and staging to treatment planning and ongoing management.

Breast surgery is one of the newest and fastest-growing surgical specialties, while the number of general surgeons handling breast procedures is diminishing. One reason for this phenomenon is that breast surgeons have taken on a role that is significantly different than the part general surgeons typically play in managing women's health: they serve as a guide through a journey full of forks in the road.

"What we do know," said Donald Lannin, MD, executive director of Yale New Haven Breast Center (New Haven, Connecticut), "is that patients treated by breast surgeons with a specialization in breast care have better outcomes than those treated by general surgeons who have less breast-specific medical training."

In the field of breast disease, "options" is the operative word. In no other area of medicine are there so many options for each phase of diagnosing and treating breast disease, rendering it a medicine of tailored personal choices.

In the area of diagnosing, a woman can have a mammogram, ultrasound, PET scan or MRI-each providing a specific view for that patient. Biopsies of suspicious lesions detected by imaging may be performed using a standard 14 Gauge needle as is used for general surgery, by core needle under stereotactic, ultrasound, or MRI guidance, or by open surgical excision.

The same is true of surgery: a patient may select lumpectomy, mastectomy with or without implants, or ablation in situ. Radiation treatments can be performed in the operating room at the time of surgery (IORT), a small dose delivered daily for 30 days (conventional radiation therapy), or accelerated brachytherapy where the dose is delivered over five days (APBI).

Various types of chemotherapy may or may not be applied, depending on the genotype of the patient. Benign breast disease such as fibroadenomas may be watched, frozen in situ, excised percutaneously or excised surgically. Obviously, each choice must be made with the guidance of a surgeon and with the individual's own clinical picture in mind.

This specialized group of surgeons assists each woman with appropriate choices for her specific disease, often using genotype information to aid with decisions.

Genetic testing is the newest tool for guiding treatment decisions in breast cancer. In 2008, 40,730 women in the U.S. died from breast cancer, second only to lung cancer deaths in women. Family history alone carries a 20% to 30% risk, while having the gene BRCA 1 & BRCA2 carries a 50% to 80% lifetime risk.

The challenge is to determine who the candidates are for genetic testing. More than 200,000 tests for hereditary susceptibility to cancer have been performed to date. Currently the guidelines for genetic testing as stated by the American Society of Clinical Oncology (Alexandria, Virginia) are when:

• There is a high likelihood of a positive test

• The test can be adequately interpreted

• The test result will influence medical management.

In managing breast disease today, there are two opportunities in which genetic testing can play an important role: screening or risk assessment and responsiveness to chemotherapy. For screening and risk assessment purposes, by far the most common type of testing is the comprehensive full sequencing of BRCA 1 and 2 gene that costs on average $3,120.

If the patient is of Ashkenazi Jewish heritage, testing for the three common mutations is in order and only costs $535. Testing for a known familial mutation at a single site is only $440 and ordering comprehensive testing is usually not necessary.

Myriad Genetic Laboratories (Salt Lake City) is currently the only lab that tests for BRCA 1 and 2. Both Medicare and many private insurers cover some or all of the testing cost, but usually only when specific criteria have been met.

Intergenetics (Oklahoma City) offers a screening or risk assessment panel consisting of 22 SNPs excluding BRCA 1 and 2 that is performed using a saliva swish test, collected much like a mouthwash specimen. They provide the patient with a lifetime risk of getting breast cancer but caution that the risks change over time so that the patient may want to repeat the test at various interims. The test results are provided to the patient's breast surgeon, who must be enrolled and trained at one of the 20 plus sites throughout the U.S.

With both of these products, the surgeon must work with the patient to create an individualized management plan based on personal and family history as well as genotype.

If a patient has been diagnosed with breast cancer, the appropriate course of endocrine and/or chemotherapy must be determined; evidence shows that certain phenotypes will not respond well to neoadjuvant chemotherapy.

Genomic Health (Redwood City, California) offers Oncotype, a gene expression test of 21 specific genes that has demonstrated the ability to predict a patient's likelihood to benefit from chemotherapy as well as her risk of experiencing a disease recurrence. In June 2007, Agendia (Huntington Beach California) received FDA clearance to perform its Mammaprint test that examines 70 gene sites and has since performed 1,696 Mammaprint profiles that have assisted patients and surgeons with their decision to pursue chemotherapy. In planning treatment, both the Mammaprint and Oncotype results provide a doctor with a clear rationale to assess the benefit of adjuvant chemotherapy.

Richard Bender, MD, chief medical director for Agenda, was a speaker in a breakfast symposium titled, "Genetic Testing: a Tool for Guiding Treatment Decisions in Breast Cancer." He said "Eventually molecular science will be able to give physicians an individual genomic profile for each patient and their tumor. The profile will predict prognosis and identify which drugs will turn pathways on or off to either kill the tumor or deprive it of key nutrients, enzymes, or co-factors required for it to grow. We will be able to use drugs that aren't 30% effective but rather 70% or more effective, taking into account an individual patient's ability to utilize a drug for their specific type of cancer."

Peter Beitsch, MD, director of the Dallas Breast Center, spoke at the same breakfast symposium and said, "Geneotype testing has changed the paradigm. We no longer care about the size of the tumor but rather its genotype. We have been treating patients as if they had the worst cancer, which means way too much chemo for many."

He added, "Now we have the ability to select those patients at highest risk, even those with the smallest tumors, and target the therapy for those who will respond."