BACKGROUND.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.METHODS.Using a database of 10,782 patients, 2685 patients were identified who experienced recurrence distantly. Clinical and biological features were analyzed in 2 ways: 1) patients who ever had versus those who never had CNS metastases, and 2) CNS metastases as the first site of recurrence versus those who had other sites. Correlations of survival after CNS metastasis with clinical and biologic features were also analyzed.RESULTS.In the ever versus never analysis, CNS metastases were significantly associated with younger age, premenopausal status, infiltrating ductal carcinoma histology (IDC), estrogen receptor (ER) and progesterone receptor (PR) negativity, low Bcl‐2, high S‐phase, aneuploidy, and altered p53. Tumor size, lymph node status, and use of adjuvant systemic therapy played little role. HER‐2 overexpression was not associated with an increased risk in these patients (none of whom were treated with trastuzumab) (P = .91). However, epidermal growth factor receptor (EGFR) overexpression was associated with increased risk (P = .02). A multivariate analysis revealed ER negativity (odds ratio [OR] 2.8, P<.001), IDC histology (OR 2.5, P = .02), and young age (P<.001) as independent factors for CNS metastases. The clinical and biologic profiles of primary tumors with CNS metastases at first recurrence did not differ from those with CNS metastases after recurrence to other sites, except for HER‐2 status. HER‐2‐positive tumors were not more likely to undergo recurrence initially in the CNS (P = .04). The median survival after CNS metastases was 5.5 months and HER‐2‐positive patients had a shorter survival.CONCLUSIONS.Younger patients with hormone receptor‐negative, highly proliferative, genomically unstable, and p53‐altered tumors were at increased relative risk for CNS metastases. HER‐2 expression and adjuvant systemic therapies did not increase this risk. Cancer 2006. © 2006 American Cancer Society.

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.

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 < or =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.

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.

Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.

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The aim of the study is to evaluate the efficacy of sertraline for controlling hot flashes in women with or at high risk of breast cancer. This was a randomized, double-blind, placebo-controlled study. All participants were asked to complete hot flash diaries. Participants reporting weekly hot flash scores >15 during baseline week underwent a 1-week single-blind placebo run-in. Those reporting hot flash score reductions >50% following placebo run-in were excluded. The remaining women received an assigned treatment for 4 weeks. Both groups' demographic and clinical characteristics were similar with a greater decline, but not statistically significant, in hot flash frequencies and scores in the sertraline-treated group compared with the placebo (P = 0.13 and P = 0.15, respectively). Emotional well-being improved significantly in the sertraline group (P = 0.041). The study failed to demonstrate effectiveness of sertraline in attenuating hot flashes in women with or at high risk of developing breast cancer who were not recommended to take hormone replacement therapy.

Neoadjuvant single agent docetaxel is effective in treating patients with large locally advanced breast cancer and clinical response is associated with improved survival. Docetaxel acts therapeutically by inducing apoptosis and this can be used as a marker of response.