Breast Cancer Clinical Trials
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Accomplishments of the NSABP in Breast Cancer

Since 1971, more than 110,000 individuals have enrolled in NSABP clinical trials. The NSABP has played a vital role in improving and indeed, in establishing, the standard treatments for breast cancer.

Over the past 50 years, the treatment of breast cancer has improved dramatically and the results of NSABP trials have been a major factor in those advances. The most visible change has been in the surgical treatment of breast cancer.

The years between 1957 and 1969 not only gave rise to the use of the clinical trials mechanism for the evaluation of adjuvant therapy in the treatment of operable breast cancer, but also demonstrated how findings from such trials could provide information for augmenting existing biological hypotheses and generating new ones.This period was particularly significant for Dr. Bernard Fisher as it introduced him to clinical trials process and stimulated his interest in tumor metastases.During the late 1950s and 1960s, Dr. Fisher's publications were submitted to more than 50 scientific journals.The information from these studies led him to formulate an alternative hypothesis that became the basis for a new generation of NSABP clinical trials.

Both Dr. Bernard Fisher and his brother, Dr. Edwin Fisher, a world renowned breast cancer pathologist, conducted a series of experiments in their laboratory at the University of Pittsburgh, which challenged the Halstedian view of cancer spread. In these animal experiments they were able to show that tumor cells spread through the lymph nodes and the blood circulation. They viewed breast cancer as a systemic disease, not just a lump in the breast. If their findings were correct, bigger operations, like the radical mastectomy, would be no more effective than less extensive procedures. This was a nice hypothesis that required proof.

He was officially appointed as the Chairman of the NSABP on May 9, 1967.  Beginning in 1971, the NSABP entered over 1,600 women in the clinical trial designed to test the effectiveness of radical mastectomy compared to the less extensive total mastectomy which limits the surgical procedure to removal of the breast. The initial results were published in 1975 and demonstrated that the radical mastectomy treated women did no better than those treated with total mastectomy. The impact was an almost overnight elimination of the use of radical mastectomy. The 25 year results published in the New England Journal of Medicine in 2003, continued to demonstrate the same findings.

These radical mastectomy results partially confirmed the new tumor spread hypothesis. For the NSABP, the next step was to evaluate the effectiveness of lumpectomy, the surgical removal of just the breast cancer lump with a rim of normal breast tissue. Beginning in 1976, over 2,100 women entered this study and were assigned to receive either the modified radical mastectomy (total mastectomy plus the removal of lymph nodes in the armpit), or lumpectomy with and without breast radiation. Now, over 20 years later, the continued follow-up of these patients showed that lumpectomy plus breast irradiation is as effective as mastectomy. Today, the majority of women who develop breast cancer have the option of choosing lumpectomy with the knowledge that the results are as good as mastectomy.

If breast cancer is a systemic disease, a theory partially confirmed in the previous studies, the next logical step would be to treat it systemically using adjuvant therapy. Adjuvant therapy (therapy in addition to surgery and radiation) can take many forms. A chemotherapy trial conducted by the NSABP in the early 1970s was the first to demonstrate that chemotherapy delivered after surgery can improve the survival of women with early stage breast cancers.

Hormonal therapies are an additional type of adjuvant treatment that are effective in breast cancers that contain certain proteins called hormone receptors. NSABP trials were among the first to demonstrate that the oral hormonal therapy, tamoxifen, could reduce the risk of breast cancer recurrence and improve survival. Tamoxifen has been the most commonly prescribed breast cancer drug in the world and this had a major impact on reducing the number of deaths due to breast cancer.  NSABP studies have also evaluated aromatase inhibitors, new hormonal therapies that appeared to be better than tamoxifen and have fewer side effects.

Newer targeted treatments for breast cancer which are neither chemotherapies nor hormonal therapies were also under evaluation. In November of 2005, the New England Journal of Medicine reported the results of an NSABP trial which demonstrated that Herceptin, a monoclonal antibody, an entirely new and exciting biologic agent, directed at a specific protein found in an aggressive form of breast cancer proved to be a hugely beneficial treatment. This study set the stage for an entirely new direction in the treatment of breast cancer. Trials with other promising agents in this family of drugs are in development at the Pittsburgh headquarters.

Since 1992, the NSABP has been actively involved in breast cancer prevention studies. In the first large scale breast cancer prevention study ever conducted, the NSABP’s P-1 trial demonstrated that tamoxifen given to healthy women at an increased risk for the future development of breast cancer, can reduce the incidence of the disease by close to 50%. These results presented in 1998, were a huge first step and established the principle that breast cancer is a preventable disease. The second step is now completed. Raloxifene, a drug long used in the prevention and treatment of osteoporosis, is thought to have the anti-cancer properties of tamoxifen while producing fewer side effects.

The Study of Tamoxifen and Raloxifene (STAR) opened in 1999, entered over 19,000 healthy post-menopausal women and was closed to entry in 2004. The initial results of this trial were announced in April 2006. The search continues for an even more effective and safer drug to prevent breast cancer.

The NSABP conducts important correlative studies in conjunction with its adjuvant trials and these have been responsible for defining many of the standard diagnostic and prognostic tools that are used today in women with breast cancer. Recently, using the NSABP Tissue Bank, which has been described by the NCI as a "national treasure”, the NSABP Foundation, in collaboration with industry, developed a 21-Gene Assay called Oncotype DX, that is used in node negative receptor positive breast cancer patients to more precisely identify those with an excellent prognosis who can be treated with only a hormonal therapy, and those with a poorer prognosis who could obtain substantial benefit from the addition of chemotherapy to their hormonal treatments. Similar efforts to more precisely target those individuals requiring specific adjuvant therapies are already underway in colon cancer.

In 1995, the NSABP Foundation was incorporated as a nonprofit corporation under the laws of the Commonwealth of Pennsylvania and shortly after, began to develop relationships with pharmaceutical and other partners in the private sector.  The Foundation began its first phase II industry trial. 

In 2008, the NSABP Foundation began its first international phase III industry sponsored research study B-44-I (BETH) to evaluate adjuvant bevacizumab plus trastuzumab/chemotherapy for the treatment of HER2+ early breast cancer. 

At the direction of the NCI, in 2014, the National Surgical Adjuvant Breast and Bowel Project is one of three cooperative groups that unite to form NRG Oncology.  The NSABP Foundation becomes the free-standing inheritor of the original group's legacy and was restructured as an academic research organization.  NSABP continues to expand its full spectrum of operational services to the private sector, from pre-clinical research through phase III trials focused on biomarker-driven studies.