Breast Cancer Metastasis: Challenges and Opportunities

Abstract

IntroductionDespite exciting progress in the understanding of breast cancer development and progression, and in the development of novel therapeutic strategies, breast cancer remains the second leading cause of cancer-related death in women, with a yearly toll of more than 40,000 deaths in the United States alone. Breast cancer-related deaths are mainly due to the "incurable" nature of metastatic breast cancer (MBC) at the current time. It is estimated that ∼6% of patients have metastatic disease at the time of diagnosis and 20% to 50% patients first diagnosed with primary breast cancer will eventually develop metastatic disease. Even with the remarkable advances in research and clinical management, the current treatment strategies for breast cancer metastasis still largely rely on the use of systemic cytotoxic agents, which frequently deteriorate the patient's life quality due to severe side effects and, in many cases, have limited long-term success. The prognosis for MBC patients is poor, with an estimated 5-year survival of only 26%. Therefore, MBC remains the most challenging task facing both cancer researcher and oncologist. To tackle this challenge, scientists and physicians of the Breast Cancer Research Program at the M.D. Anderson Cancer Center held a symposium to (a) provide a better understanding of breast cancer metastasis at the molecular and cellular level; (b) introduce cutting-edge technologies in metastatic breast cancer detection, including clinicopathologic detection, circulating tumor cells (CTC) detection, and advanced imaging; and (c) solicit innovative ideas in basic, translational research and clinical patient management. The symposium led to a positive consensus notion that we will be able to prevent, and to a lesser degree, treat metastasis and ultimately save most patients from metastatic deaths in the foreseeable future. The Challenges of Breast Cancer Brain MetastasisUnderstanding the molecular and biological basis of metastasis is essential for paving the way to conquering it. Dr. Patricia Steeg (National Cancer Institute, Bethesda, MD) set the stage on the challenges of understanding metastasis in her keynote speech: A Molecular Portrait of Brain Metastasis of Breast Cancer. Brain metastasis represents a devastating consequence of breast cancer, with a particularly dismal prognosis of ∼80% mortality within 1 year of diagnosis. The classic tools in treating brain metastasis, including neurosurgery, stereotactic radiosurgery, or whole brain radiation, are partially effective in treating large macrometastasis; however, these tools have limited effects on controlling small micrometastasis, many of which will grow and eventually become deadly to patients. Therefore, novel molecular therapies to eliminate or stabilize micrometastasis are urgently needed. However, the development of effective chemotherapy in treating brain metastasis has been especially challenging due to the limited permeability of the blood-brain barrier, which is considered a "sanctuary site" for tumor cells. To study b...

Breast Cancer in Women: Recurrence and Survival at Five Years

“…Therefore, according to the authors of the aforementioned study, metastatic breast cancer still presents a poor prognosis. 21 In regard to rates of metastasis and loco-regional recurrence, this study's findings show 25.2% and 6.5%, respectively. After follow-up of 2,534 women with breast cancer in Poland for six years, 35.0% experienced metastasis, 14.0% loco-regional recurrence and 39.0% died.…”

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

“…The remaining patients, diagnosed with apparently localized primary breast cancer, have a 20-50% chance of developing metastatic disease later, sometimes after more than two decades (Lu et al 2009).…”

Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer.

“…Of these women diagnosed with breast cancer, approximately 6% had de novo stage IV disease and 20% to 50% diagnosed with primary breast cancer will go on to develop metastatic disease with an estimated five year survival of 26% (2). One of the biggest clinical challenges faced by women with metastatic breast cancer is the development of brain metastases, with a reported incidence ranging from 10% to 30% (3)(4)(5) and typically associated with an approximately 80% mortality within one year of diagnosis (2).…”

“…Of these women diagnosed with breast cancer, approximately 6% had de novo stage IV disease and 20% to 50% diagnosed with primary breast cancer will go on to develop metastatic disease with an estimated five year survival of 26% (2). One of the biggest clinical challenges faced by women with metastatic breast cancer is the development of brain metastases, with a reported incidence ranging from 10% to 30% (3)(4)(5) and typically associated with an approximately 80% mortality within one year of diagnosis (2). Over the last decade evidence has emerged that the incidence of brain metastases appears to be increasing, probably attributed to the fact that with the introduction of newer chemotherapeutic and targeted agents (e.g trastuzumab) women with breast cancer are living long enough to develop brain metastases coupled with superior imaging techniques leading to improved detection rates (6)(7)(8)(9).…”

“…Each subtype is associated with a distinct prognostic outcome and unique predilections for sites of recurrence highlighted by the fact that the incidence of brain metastases among women with HER2-positive and basallike subtype cancer exceeds one third of patients, while the incidence is notably lower among women with breast cancer of luminal subtype (2). Despite the high incidence of brain metastases among women with HER2-positive breast cancer, the recent introduction of trastuzumab into their treatment protocols has not only increased the time to development of brain metastases but has significantly improved survival following the development of brain metastases (14,15).…”