SABCS Preview: Prevention, Screening, and Neoadjuvant Therapies

C. Kent Osborne, MD

Many important issues will be addressed in the presentations at the 36th San Antonio Breast Cancer Symposium (SABCS), held annually in San Antonio, Texas, this year December 10-14. Presentations at the international symposium will tackle key topics and questions regarding the treatment of breast cancer.

The symposium co-directors, Peter Ravdin, MD, PhD, University of Texas Health Science Center, San Antonio; Carlos L. Arteaga, MD, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee; and C. Kent Osborne, MD, Baylor College of Medicine, Houston, Texas, recently highlighted key presentations planned for the upcoming meeting at an organized press conference.

Osborne highlighted several presentations that will address the issue of overdiagnosis as a result of mammography screening. Although such screening has been shown to be effective in reducing deaths from breast cancer in certain subpopulations of women, false-positive rates are not zero and can lead to invasive follow-up procedures and anxiety for patients. Screening also leads to diagnosis of cancers that may not ever become a significant risk to the patient’s health.

An international consortium of the American Cancer Society and groups from other countries have addressed why different studies have led to different conclusions. The study re-evaluated four major reviews from the United Kingdom, United States, and Europe using the same approach (abstract S1-10). “I believe this study is going to come up with some interesting data on the value of mammography and will also address whether overdiagnosis is really a problem or not, with regard to these mammography studies,” said Osborne.

Addressing the issue of overtreating certain subgroups of patients, the results of the Post-operative Radiotherapy In Minimum-risk Elderly 2 (PRIME-2) trial will be presented (abstract S2-01). The study randomized women aged 65 years or older to either post-surgery radiation or no radiation to assess the role of radiotherapy in this older group of women who are lumpectomy candidates. “These results will give us more data on whether women need radiation therapy, which has been the standard for all women with breast cancer who have had a lumpectomy,” said Osborne.

Two other studies will address whether or not surgery on the primary tumor in the breast is necessary for women who are diagnosed with metastatic breast cancer. Unlike previous retrospective trials addressing this topic, the two trials to be presented will be prospective and randomized. One study randomized 350 patients with metastatic breast cancer who have received and responded to chemotherapy to either surgery with subsequent radiation therapy or to no follow-up intervention (abstract S2-02). The trial aims to help clinicians understand whether or not women with breast cancer that has spread to other parts of the body can benefit from localized surgery and radiation therapy. The second trial randomized patients with metastatic breast cancer who are treatment-naïve to receive either surgical resection of their primary tumor or no resection (abstract S2-03). All patients were then treated for their metastatic disease. “These two trials will go a long way in helping clinicians to decide whether patients should go through surgery to remove the tumor in their breast when they have metastatic cancer,” said Osborne.

In the metastatic setting, a combination trial will address one possible way to curb resistance in treatment of hormone- positive disease. For women with hormone-positive metastatic disease, results will be presented of a trial that combined the aromatase inhibitor letrozole with dasatinib, a drug that targets a potential resistance pathway (abstract S3-07). According to Osborne, this will be an important study to show whether or not this combination that simultaneously blocks the estrogen pathway and one escape pathway could improve outcomes in this patient population.

Selected Upcoming Abstracts at SABCS

S1-10: Smith et al. Disparities in the estimates of benefits and harms from mammography: are the numbers really different?

S2-01: Kunkler et al. The PRIME 2 trial: wide local excision and adjuvant hormonal therapy ± postoperative whole breast irradiation in women ≥ 65 years with early breast cancer managed by breast conservation.

S2-02: Badwe et al. Surgical removal of primary tumor and axillary lymph nodes in women with metastatic breast cancer at first presentation: a randomized controlled trial.

S2-03: Soran et al. Early follow up of a randomized trial evaluating resection of the primary breast tumor in women presenting with de novo stage IV breast cancer; Turkish study (protocol MF07-01).

S3-07: Paul et al. Letrozole plus dasatinib improves progression-free survival (PFS) in hormone receptor-positive, HER2-negative postmenopausal metastatic breast cancer (MBC) patients receiving first-line aromatase inhibitor (AI) therapy.

S1-01: Piccart-Gebhart et al. The association between event-free survival and pathological complete response to neoadjuvant lapatinib, trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06).

S1-02: Hurvitz et al. Final analysis of a phase II 3-arm randomized trial of neoadjuvant trastuzumab or lapatinib or the combination of trastuzumab and lapatinib, followed by six cycles of docetaxel and carboplatin with trastuzumab and/or lapatinib in patients with HER2+ breast cancer (TRIO-US B07).

S3-01: Cuzick et al. First results of the International Breast Cancer Intervention Study II (IBIS-II): a multicentre prevention trial of anastrozole versus placebo in postmenopausal women at increased risk of developing breast cancer.

Many of the trials of interest to clinicians that will be presented at the symposium are neoadjuvant breast cancer studies. The FDA recently provided guidance on the use of pathologic complete response (pCR) as a clinical trial endpoint in neoadjuvant treatment prior to surgery. Neoadjuvant systemic therapy aims to reduce the probability that patients will have remaining metastatic disease after surgical removal of their tumor, and is a way to assess tumor response in vivo that could improve the development of particularly active drugs. “Knowing the neoadjuvant effects on the tumor before surgery may predict the long-term effects on micro-metastatic disease,” said Ravdin.

Two presentations will analyze results of neoadjuvant therapy in women with HER2-positive disease. A followup analysis of the NeoALTTO trial will provide information on the correlation of pCR in the breast to long-term eventfree survival (abstract S1-01). The trial randomized women with HER2-positive primary breast cancer to receive lapatinib, trastuzumab, or the combination, followed by surgery, chemotherapy, and 1 year of the same therapy that the patient received in the neoadjuvant setting.

A second neoadjuvant trial highlighted by Arteaga examined a novel chemotherapy combination of docetaxel and carboplatin in addition to lapatinib, trastuzumab, or both (abstract S1-02). “This trial looks similar to NeoALTTO, but the importance here will be the new chemotherapy backbone,” said Arteaga. “The safety data will be important to learn from here.”

“I think these two studies may contribute to the body of work that may support the neoadjuvant study approach without the need to do costly, long adjuvant studies,” said Arteaga. The implication is that this approach could accelerate the time it takes to approve clinically active drugs, he said.

In the area of breast cancer prevention, the IBIS-II trial is addressing prevention using the aromatase inhibitor anastrozole in women who are at high risk for developing breast cancer (abstract S3-01). This United Kingdom study randomized 3800 patients to either anastrozole or placebo, and will address the efficacy of the drug to lower estrogen levels in postmenopausal women at risk. Importantly, the trial will address the tolerability of side effects associated with the drug for women who do not have breast cancer. One of the problems with prevention is that you need a drug that is relatively without side effects because most women will not be diagnosed with breast cancer, according to Osborne. “I would be surprised if this study is negative,” he added. “[The results] will add additional information on the value of using estrogen deprivation therapy for breast cancer prevention.”

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