Breast Cancer

Anthracyclines are among the most effective and widely prescribed anticancer agents. They were first isolated from cultures of Streptomyces peucetius by Dr. Federico Arcamone in the early 1960s.[1] Anthracyclines have since become an essential component of breast cancer treatment, and their use in combination regimens as adjuvant therapy is the standard of care for most women with early-stage disease.[2] Two commonly used anthracyclines in breast cancer are doxorubicin and epirubicin, a semisynthetic derivative of doxorubicin.

One-fifth of women who should receive radiation after a mastectomy are not getting this potentially lifesaving treatment, according to a new study from researchers at the University of Michigan Comprehensive Cancer Center.

Recent results from prospective, controlled trials, specifically evaluating strategies for preventing or reducing the severity of the dermatologic effects of EGFR inhibitors, represent the first step toward an evidence-based approach to the prevention and management of these important effects.

The review by LoRusso is a critical update to what could be considered the most significant dermatologic toxicity in modern oncology. This increased importance of dermatologic toxicities to epidermal growth factor receptor (EGFR) inhibitors can be attributed to several factors: 45% to 100% of patients will develop a papulopustular rash; the rash occurs in cosmetically sensitive areas (the face and upper trunk); it is associated with symptoms of pain and pruritus; and superinfections occur in approximately 30% of patients receiving these agents-all of which lead to dose modification by 76% and discontinuation by 32% of oncologists.

Epidermal growth factor receptor (EGFR) inhibitors have emerged as important drugs in cancer therapy, providing a proven survival advantage for some patients with non–small-cell lung cancer, colorectal cancer, head and neck cancer, and pancreas cancer.

Breast cancer is the most common female malignancy in the Western world. Two-thirds of all breast cancers are estrogen receptor (ER)-positive, a phenotypic characteristic that is prognostic of disease-free survival and predictive of response to endocrine therapy.

Historically, breast tumor classification and therapeutic decisions have relied on immunohistochemical (IHC) techniques for characterizing biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and the epidermal growth factor receptor 2 (HER2), as described in the review by Ma and colleagues. However, these markers have been found to be inadequate for fully predicting a patient’s response to a given breast cancer treatment such as endocrine therapy.

This article reviews ongoing progress in the effort to identify predictors of endocrine therapy responsiveness for breast cancer and discusses the value of “pre-treatment” vs “on-treatment” tumor profiling for predicting outcomes.

Luteinizing hormone-releasing hormone analogs (LHRHa) are often used alone or in combination with tamoxifen to suppress ovarian function in premenopausal women with endocrine-responsive breast cancer. However, aromatase inhitiors (AIs) are now the preferred first-line endocrine treatment for postmenopausal women with breast cancer.

SAN ANTONIO-Data presented at SABCS 2008 by the ATAC Trialists’ Group extends the value of the Oncotype DX Recurrence Score in assessing risk of distant recurrence in breast cancer patients receiving an aromatase inhibitor.

Based on the 1995 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Overview, tamoxifen is now the standard of care for premenopausal women with hormone receptor–positive early breast cancers.[1]

Developed over a century ago,[1] endocrine therapy remains the most effective and the most clearly targeted form of systemic therapy for breast cancer. Endocrine treatments work best in women whose tumors are positive for estrogen receptors (ER) and/or progesterone receptors (PR).

The optimal endocrine therapy for premenopausal women with hormone receptor–positive early breast cancer remains elusive. Dr. Pritchard presents a thoughtful review of this important topic, including the historic context for the current controversy regarding the utility of ovarian suppression (either by medication or permanent ablation) in the adjuvant treatment of young women with breast cancer.

Patients with operable triple-negative breast cancer are at increased risk for recurrence if their tumor has higher levels of a protein-encoding gene implicated in migration, proliferation, and other cellular processes, reported Joseph A. Sparano, MD, from the Eastern Cooperative Oncology Group.

Lapatinib (Tykerb) plus letrozole (Femara) may delay disease progression in metastatic breast cancer patients, according to an international phase III trial. Patients who benefited from the protocol were those who overexpressed the HER2/neu protein and the epidermal growth factor receptor and were also hormone receptor-positive.

Neoadjuvant therapy that includes trastuzumab (Herceptin) prolongs event-free survival and has an acceptable safety profile in women with HER2-positive locally advanced breast cancer, based on results from the largest trial testing such therapy in this setting.

Expression of the microtubule-binding protein Tau is not a reliable means of selecting breast cancer patients for adjuvant paclitaxel chemotherapy, investigators from Houston’s M.D. Anderson Cancer Center stated, adding that while Tau expression does predict survival, it does so in an unexpected way.

Data presented by the ATAC Trialists’ Group extends the value of the Oncotype DX Recurrence Score in assessing risk of distant recurrence in breast cancer patients receiving an aromatase inhibitor.

The cure for cancer lies in the biology of circulating and disseminating tumor cells that, unfortunately, evade detection and treatment very easily, according to one of the world’s leaders in the field. In a plenary lecture, Klaus Pantel, MD, described the properties and clinical relevance of the cells that eventually cause metastatic relapse but remain elusive at primary diagnosis.

The concept of bisphosphonates as anticancer agents took a leap forward this week thanks to results from the AZURE trial. Investigators from the UK reported that patients receiving zoledronic acid along with neoadjuvant chemotherapy experienced a doubling in complete pathological response.

Oncology NEWS International guest editor Dr. Andrew D. Seidman recommends SABCS 2008 lectures on modern molecular science, molecular profiling, and the American Association of Cancer Research distinguished lectureship in breast cancer research.

Insight into the molecular workings of HER2-positive breast cancer has paved the way for targeted agents that are showing great promise in clinical trials, according to a presentation at SABCS 2008. José Baselga, MD, from Barcelona, offers a primer on pertuzumab, trastuzumab-DM1, heat shock protein 90, and other agents that will provide “tremendous opportunity” in HER2-positive cancer treatment.

Emerging knowledge about breast cancer biology must be integrated into clinical trials in order to personalize treatment in patients with early breast cancer. Two speakers at an educational session on clinical trial design discussed our advancing understanding of basic science and the ways in which that can change and refine the design of clinical trials.

Estrogen-receptor–positive advanced breast cancer patients who have become resistant to endocrine therapies can derive clinical benefit from 6-mg daily doses of estradiol, according to a phase II study conducted at Washington University in St. Louis.

Combining endocrine therapy with signal transduction inhibition is an effective means of overcoming endocrine resistance in at least some populations of patients with breast cancer. Stephen R.D. Johnston, MA, PhD, director of clinical research and development at the Royal Marsden Hospital in London, discussed the data on this emerging strategy during an SABCS plenary lecture.