Breast Cancer

Over 40 million men and women in the United States have osteoporosis and low bone mineral density (BMD), placing them at risk for adverse skeletal events such as fractures and their sequelae. There are over 12 million cancer survivors in this country. Of these, 22% were diagnosed with breast cancer and 17% with prostate cancer.[1,2] Because cancer therapies can adversely influence bone health, these survivors are at particular risk for skeletal complications. Cancer therapies associated with bone loss include hormone deprivation therapies such as aromatase inhibitors, ablative surgical procedures that induce hypogonadal states, and premature menopause induced by chemotherapy.[3,4]

Many women continue to experience pain and sensory disturbance up to three years after breast cancer treatment, according to Danish researchers, who found that younger women in particular reported persistent pain. They called for further strategies for improving pain management after breast surgery.

This article will review and summarize the current data regarding the influence of the major cytochrome P450 2D6 (CYP2D6) genotypes and CYP2D6 inhibitors on tamoxifen metabolism and clinical efficacy. We will discuss the clinical relevance and limitations of this data and how to best incorporate our current understanding of CYP2D6 genotyping into our clinical practice and discussions with patients.

In the post–Human Genome Project era, “personalized medicine” has become a buzzword. Health-care professionals increasingly have access to gene sequence data, with the promise that this information will improve the health of the individual. In the area of breast oncology, the study of genetic markers associated with clinical outcome has been a relative success story.

The promise of pharmacogenetics is personalization of therapy for individuals through refinement of the risk/benefit profile of pharmaceuticals based on inherited gene mutations. Classic examples of the impact of pharmacogenetics in clinical practice include variants in dihydropyrimidine dehydrogenase and treatment with fluorouracil.

A 56-year-old woman was referred to our institution for a left nephroureterectomy after the diagnoses of a nonfunctioning left kidney and noninvasive papillary urothelial carcinoma of the distal left ureter (Ta grade 1). Following the procedure, surveillance cystoscopy and computed tomography (CT) scan of the abdomen and pelvis demonstrated a large bladder tumor with pan-urothelial extension.

The targeted combination of lapatinib (Tykerb) plus trastuzumab (Herceptin) led to a median overall survival of 14 months in women with refractory metastatic breast cancer, according to an updated analysis of the phase III EGF104900 trial. A bonus: The majority of toxicities were low-grade.

Despite a better dose loading schedule and compelling preclinical data, the combination of fulvestrant and anastrozole did not demonstrate any advantage in first relapse of hormone receptor-positive breast cancer, according to first results from the FACT trial.

Researchers in Taiwan and China found that alternating mammography and ultrasound led to a higher cancer detection rate in women aged 40-49. Meanwhile in the UK, a group from West Midlands Research Collaborative have made a case for starting screening at age 40 in certain ethnic groups. Finally, German investigators assessed the value of semi-annual ultrasound exams in high-risk women.

The RIBBON-2 trial met its primary endpoint to prolong progression-free survival, making the bevacizumab-chemotherapy combination a new treatment option, said principal investigator Adam Brufsky, MD. The trial continued the evaluation of bevacizumab plus chemotherapy to treat metastatic breast cancer after previous treatment failures.

Along with many other health issues, obese breast cancer patients face a particularly grim prognosis, with an amplified risk of recurrence and an increased risk of dying of the disease, according to results from a long-term, large-scale study in a Danish population. The researchers also noted that a larger body habitus negatively impacted treatment results.

Denosumab prevented more events, was better tolerated, and was more convenient for breast cancer patients with skeletal metastasis, according to results from a randomized double-blind trial that matched the RANK ligand inhibitor against zoledronic acid.

Exemestane alone and exemestane following tamoxifen, are equally appropriate treatment options, according to results from TEAM, the first trial prospectively powered to test the superiority of five years of aromatase inhibitors compared with a specific sequential strategy in postmenopausal women with endocrine-sensitive breast cancer.

Ultrasound is an effective way to monitor lymph node recurrence after breast cancer surgery, South Korean researchers reported. Regional lymph node recurrence affects just 2% to 16% of patients with any stage of breast cancer, but is difficult to manage and associated with poor prognosis.

The skeletal health of pre-menopausal women with estrogen receptor-negative breast cancer took a beating after six cycles of doxorubicin (Doxil)/cyclophosphamide (A/C) chemotherapy.

In their recent commentary (Oncology 23:639-641, 2009), Labriola and colleagues reviewed the data on “natural” hormone replacement and breast cancer risk. The “natural” agents were bioidentical and phytoestrogen supplements to manage vasomotor symptoms in breast cancer patients.

Our commentary in the July 2009 issue of ONCOLOGY concluded that the current level of evidence for safety and efficacy of “natural” hormone replacement therapy (NHRT) is not conclusive.

Dr. Otis W. Brawley took a courageous stand late last week, one he has taken many times before, but which had until then gone all but unnoticed. Responding to a Journal of the American Medical Association article detailing the scientific and medical limitations of breast and prostate screening, the chief medical officer of the American Cancer Society acknowledged that “in the case of some screening for some cancers, modern medicine has overpromised.”

Removal of the primary breast tumor in women whose cancer has already metastasized can have a significant effect on their survival, Dutch researchers have found. Dr. Jetske Ruiterkamp, a surgical resident from the Jeroen Bosch Hospital, Den Bosch, The Netherlands, working under the supervision of Dr. Miranda Ernst, told Europe’s largest cancer congress, ECCO 15/ESMO 34, in Berlin that her research meant that women who were diagnosed at a late stage of the disease could expect to survive longer.

Data from the Austrian Breast and Colorectal Cancer Study Group (ABCSG)-24 study presented at the joint 15th ECCO and 34th ESMO congress in Berlin, show that adding capecitabine (Xeloda) to anthracycline- and taxane-containing regimens prior to surgery completely eradicated the tumor in 24% of women with HER2-positive or HER2-negative early breast cancer. This is an impressive finding since the proportion of women achieving total tumor eradication with standard chemotherapy for HER2-positive or HER2-negative early breast cancer is less than 20% (range = 6%–18%).

Breast cancer is the most common newly diagnosed malignancy among American women. In 2008, an estimated 182,460 new cases of invasive breast cancer, and an additional 67,770 cases of in situ cancer were diagnosed. Approximately 40,480 women will die from breast cancer each year.

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc, announced the full results from their first collaborative group-sponsored randomized, double-blind, placebo-controlled phase II trial showing that sorafenib (Nexavar) tablets in combination with the oral chemotherapeutic agent, capecitabine (Xeloda), significantly extended progression-free survival in patients with advanced breast cancer.

ORLANDO-Breast cancer experts gathered at ASCO 2009 to answer five important questions about anthracyclines, taxanes, HER2-positive disease, trastuzumab (Herceptin), and anti-VEGF agents. Their key message for adjuvant therapy: One size does not fit all. The participants were:

Long-term tamoxifen use among breast cancer survivors is associated with a more than fourfold increased risk of ER-negative cancer in the contralateral breast, according to the investigators at Seattle’s Fred Hutchinson Cancer Research Center.

Hologic, Inc, recently announced the US Food and Drug Administration (FDA) cleared the Company’s 510K application for the MammoSite ML radiation therapy system. With its multilumen design, this new device gives radiation oncologists the ability to shape the radiation dose for typical cases and treat patients who are otherwise not appropriate candidates for traditional brachytherapy.