GUIDELINES FOR BREAST CANCER UPDATED

NCCN 2009: Guidelines for Breast Cancer Updated

March 19, 2009 (Hollywood, Florida) — Genetic counseling is now recommended for women with either ductal carcinoma in situ or early invasive breast cancer when genetic testing indicates a high risk for hereditary breast cancer, said Beryl McCormick, MD, from the Sloan-Kettering Cancer Center, in New York City, in a presentation here at the National Comprehensive Cancer Network (NCCN) 14th Annual Conference.

Dr. McCormick said that the new NCCN recommendation was supported by a 2007 study that showed a dramatic increase in the decision to opt for a bilateral mastectomy (from 4% in 1998 to 11% in 2003) by women who present with unilateral disease and have a high genetic risk. "I suspect that if we looked again, the percentage would be up even higher," she said. The new recommendation will allow these women to make more informed decisions about local treatment.

"We are finding now that, in high-risk women in these populations, genetic testing following diagnosis can often lead to decisions to treat both the affected and unaffected breast," said Dr. McCormick.

She presented the updates to the NCCN's breast cancer guidelines along with Stephen Edge, MD, from Roswell Park Cancer Institute, in Buffalo, New York. The new counseling recommendation was 1 of a host of changes/additions, which include:

• revision of the status of a radiation boost in women with early invasive breast cancer to optional;
• new pathway for mastectomy in recurrent disease;
• use of magnetic resonance imaging (MRI);
• breast-reconstruction guidelines;
• local therapy in women who present with metastatic disease;
• ranking of chemotherapy and hormone-therapy options.

The breast cancer panel is the largest group of experts within the NCCN and meets annually for 3 days to review developments in breast cancer and the related guidelines, said Dr. McCormick.

Changes Regarding Radiation Therapy

In previous guidelines, women with early-stage breast cancer were all advised to receive a boost of radiation to the whole breast (by photons, brachytherapy, or electron beam). The guidelines now make that boost optional.

The revision is based in part on a large EORTC study, which indicated that the boost did not provide a significant advantage in preventing recurrence over 8 years for women older than 60 years. However, the advantage was "highly significant" in women younger than 40, said Dr. McCormick. She also noted there was some advantage to the boost in women aged 41 to 50 years and 51 to 60 years, but it was not as dramatic as it was for the young women. Hence, the guidelines present the boost as optional now, she said.

For clinicians treating women who have locally recurrent disease, there is now a new pathway to consider. If a woman has had no previous radiation therapy and was initially treated with mastectomy, the clinician should now consider (in addition to either surgical resection or total mastectomy and axillary dissection) another option — surgical resection plus radiation therapy to the chest wall and internal mammary nodes, said Dr. McCormick.

Surgery for Women Who Present With Metastatic Disease

A "very important footnote" to the new guidelines is in the treatment of women who present with metastatic disease, noted Dr. McCormick. These women may benefit from the performance of local breast surgery and/or radiation therapy. "Generally, this palliative local therapy should be considered only after response to initial systemic treatment," she said.

The support for this addition to the guidelines is from several recent retrospective studies that demonstrated improved survival when the primary tumor was removed with negative margins, she added.

"In the past, surgery was reserved for women with metastatic disease who progressed," said Dr. Edge. However, data from the National Cancer Data Base show that increasing numbers of women are now undergoing surgery at the time of the initial metastatic diagnosis (rather than when they progress). In women who are left with clear margins, this approach doubles the median survival time to about 2 years, compared with 12 months in women who have no surgery.

Dr. Edge also noted that these different approaches to surgery in the treatment of women who present with metastatic disease would be "best addressed" with a controlled trial, but this has not yet been done.

Guidance on Use of MRI

Guidance on the use of MRI is also addressed in the new NCCN document. However, the guidance is only a footnote and has not yet been codified into pathways, emphasized Dr. Edge. "This is a rapidly evolving area of practice and there is no firm consensus about MRI," Dr. Edge acknowledged.

Nevertheless, the new footnote spells out the role of MRI in breast cancer. MRI is now recommended for screening women at high risk, for evaluating the extent of disease (especially screening for second lesions), for defining response to adjuvant therapy, and for evaluating breasts with an axillary node with adenocarcinoma and a normal mammogram.

"Lesions identified by MRI must be biopsied because of the high rate of false positives," Dr. Edge emphasized, noting that about 75% to 80% of the lesions identified on MRI are benign. He also noted that in 1 study of women with breast cancer undergoing an MRI in case of a second lesion, the MRI caught more false positives (24%) than second tumors (10%).

MRI may also lead to increased use of mastectomy, Dr. Edge said. However, there is no evidence that these MRI-related mastectomies have any impact on local recurrence or survival in women, he emphasized.

Adjuvant Therapy and Breast Reconstruction

In its section on adjuvant chemotherapy, the NCCN's breast cancer guidelines now rank the therapies. "It's not just pick-as-you-choose anymore," said Dr. Edge.

For women who are not treated with trastuzumab (Herceptin, Genentech) regimens, the preferred regimens are:

• TAC (docetaxel [Taxotere] plus doxorubicin [Adriamycin] plus cyclophosphamide);
• dose-dense AC (doxorubicin plus cyclophosphamide) followed by paclitaxel every 2 weeks;
• TC (docetaxel plus cyclophosphamide);
• AC (doxorubicin plus cyclophosphamide).

For women who are treated with trastuzumab, the preferred adjuvant regimens are:

• AC (doxorubicin plus cyclophosphamide) followed by T (docetaxel) plus concurrent trastuzumab;
• TCH (docetaxel, carboplatin, trastuzumab).

The new guidelines also now have a section on the principles of breast reconstruction following surgery. In general, these guidelines apply only to surgeons who have experience with both plastic surgery and breast cancer surgery, said Dr. McCormick. They note that reconstructive surgery can be completed either at the time of mastectomy or subsequently.