Yee Lu Tham

Primary breast cancer phenotypes associated with propensity for central nervous system metastases

There is anecdotal evidence that the incidence of central nervous system (CNS) metastases in breast cancer patients is increasing. It is unclear whether specific tumor biological properties or the use of systemic therapies influence this risk.

Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients

PURPOSE Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. PATIENTS AND METHODS Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m(2) every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 microg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). RESULTS From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G(2)M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. CONCLUSION A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment.

The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane

Objective:Adjuvant chemotherapy in premenopausal women with breast cancer may induce amenorrhea, which can affect fertility, choice of hormonal therapy, and increase the risk of late toxicity. The incidence of chemotherapy-induced amenorrhea (CIA) resulting from doxorubicin and cyclophosphamide (AC) followed by a taxane (T) is poorly characterized. Methods:We retrospectively surveyed women who were premenopausal and less than age 50 at initiation of chemotherapy to determine the rates of CIA in women receiving AC followed by T compared with AC alone. Results:One hundred ninety-one eligible women completed the survey. The rate of CIA in women who received AC followed by T was 64% (95% confidence interval [CI] = 55–72%) compared with 55% (95% CI = 43–66%) in AC alone. As expected, CIA rates were higher in older than younger women (82% vs. 55%, P = 0.004). Multivariate logistic regression analysis revealed that age >40 was associated with a 4.6-fold increased risk of CIA (95% CI = 1.7–12.1, P = 0.002). It also revealed that receiving T after AC was associated with an odds ratio of 1.9 for CIA as compared with receiving AC alone (95% CI = 1.0–3.5, P = 0.05). Despite ≥6 months of amenorrhea, many women ≤40 resumed menses (40%). CIA was more likely to be irreversible in those >40. The addition of taxanes did not alter the rate of reversibility for the group as a whole (P = 0.36). Conclusions:Older age and the addition of taxane to AC increased the risk of CIA and the amenorrhea was more likely to be irreversible for women >40. Women ≤40 often resume menstruation even after 6 months of amenorrhea, and the addition of T does not play a role. Subsequent resumption of menstrual function must be considered when initiating appropriate hormonal therapy.

Self-blame, self-forgiveness, and spirituality in breast cancer survivors in a public sector setting

Cognitive appraisal affects adjustment to breast cancer. A self-forgiving attitude and spirituality may benefit breast cancer survivors who blame themselves for their cancer. One hundred and eight women with early breast cancers completed questionnaires assessing self-blame, self-forgiveness, spirituality, mood and quality of life (QoL) in an outpatient breast clinic. Women who blamed themselves reported more mood disturbance (p < 0.01) and poorer QoL (p < 0.01). Women who were more self-forgiving and more spiritual reported less mood disturbance and better QoL (p’s < 0.01). Interventions that reduce self-blame and facilitate self-forgiveness and spirituality could promote better adjustment to breast cancer.

Reversible and irreversible cardiac dysfunction associated with trastuzumab in breast cancer.

One of the newest agents used in the treatment of breast cancer is trastuzumab (Herceptin®), a new recombinant DNA-derived humanized monoclonal antibody against the proto-oncogene, HER-2/neu gene product. However, despite its proven clinical efficacy, serious adverse effects leading to trastuzumab-induced cardiomyopathy have been described in up to 27% of patients receiving combination therapy with anthracyclines [1]. There has been little published on the clinical syndrome of trastuzumab-induced cardiomyopathy. We describe three cases, of both reversible and irreversible cardiomyopathy, associated with the use of this novel and effective agent in HER-2 overexpressing breast cancer.

A Phase II Trial of Capecitabine Concomitantly With Whole-Brain Radiotherapy Followed by Capecitabine and Sunitinib for Brain Metastases From Breast Cancer

BACKGROUND Brain metastasis from breast cancer presents a significant threat to womens health and quality of life. Capecitabine and sunitinib have shown some activity in this setting; therefore, we conducted a single-arm phase II trial with these agents. METHODS Patients with breast cancer and central nervous system (CNS) metastases received whole-brain radiotherapy concurrently with capecitabine (1,000 mg/m(2) per day for 14 consecutive days), followed by concomitant capecitabine (2,000 mg/m(2) per day for 2 weeks followed by a 1-week break) and sunitinib (37.5 mg daily, continuously). The primary endpoint was progression-free survival (PFS). RESULTS Of 25 planned patients that would be required to detect a 4-month improvement (from 5 to 9 months) in median PFS with 80% power, 12 were enrolled, and the study was then closed for slow accrual. Median PFS was 4.7 months, and median overall survival was 10 months. In the CNS, 25% had progressive disease, and 83% experienced extra-CNS progression. The most common side effects were fatigue and nausea. CONCLUSION In 12 evaluable patients studied, concurrent capecitabine and whole-brain radiation followed by capecitabine and sunitinib did not extend PFS over historical rates and was associated with significant toxicity. Our study was small and closed due to slow accrual.