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Dose-dense chemotherapy has made a significant contribution to the adjuvant treatment of breast cancer. One way of achieving dose-density is through the use of sequential therapy with noncross resistant therapies to cause cell kill in tumors composed of heterogeneous cells. Another way to achieve this is to shorten the inter-treatment interval to minimize the re-growth of tumor cells, thus allowing for more effective cell killing. Several trials have tested this concept with the majority demonstrating improved efficacy with a dose-density when compared with the traditional schedule. One such notable trial was CALGB 9741 that showed that when dose size and cycle numbers were kept constant, shortening the interval between each chemotherapy dose, with granulocyte-colony stimulating factor support, significantly improved disease-free and overall survival. This important and practice-changing trial led to the wide adoption of dose-dense chemotherapy and formed the basis of many subsequent studies, including allowing for the addition of biologic and targeted agents with excellent safety profile. [ABSTRACT FROM AUTHOR]

Taxanes are now routinely used in conjunction with radiation therapy (RT) as adjuvant therapy for breast cancer. Recent publications have reported several cases of radiation pneumonitis (RP) in patients receiving RT and taxane chemotherapy, thus raising concern as to the safety of this combination. To decrease the potential risk of RP, we sequenced RT after taxane chemotherapy with a target interval of 3–4 weeks in two consecutive institutional breast protocols. Forty patients were treated on two adjuvant systemic protocols consisting of modified radical mastectomy ( n = 9) or breast-conserving surgery ( n = 31), followed by adjuvant doxorubicin, cyclophosphamide, and a sequential taxane (ACT), followed by RT. All patients had either node-positive or high-risk node-negative breast cancer and were treated between October 2000 and September 2002. Postmastectomy, a median dose of 5040 cGy was delivered to the chest wall. After breast-conserving surgery, a median dose of 4680 cGy was delivered to the breast plus a 1400 cGy boost to the surgical cavity. Information regarding RP was gathered retrospectively by reviewing patient records. With a median follow-up of 28 months (range 6–42 months), no cases of clinical RP were identified and no local failures had occurred. The median time interval for all patients between the completion of chemotherapy and the initiation of RT was 34 days (range 5–70 days). At the latest follow-up, 2 patients were diagnosed with metastatic disease and 38 patients were without evidence of disease. Sequencing of RT after taxane therapy with a target interval of 3–4 weeks does not appear to result in increased pulmonary toxicity and is associated with good local control. [ABSTRACT FROM AUTHOR]

Patients with breast cancer, which lacks ER, PR, and HER2; 'triple negative' (TNBC), are at increased risk of brain metastases (BMs). However, the impact of modern therapy on the risk of BMs and outcomes remains largely unknown. In this retrospective, single-institution study we assessed the incidence of BMs, the therapeutic options, and overall survival, in a recent cohort of patients with TNBC. Women diagnosed with early stage TNBC from January 1, 1998 to December 31, 2007 were identified through institutional databases. Electronic medical records were reviewed to assess patterns of recurrence, treatment, and survival. In total, 1,323 patients, median age 53 years (range 20-91), were identified. There were 298 patients (23%) who developed metastatic disease, of whom, 99 (33%) developed BMs, representing 7.5% of the entire cohort. Following BM diagnosis, treatment consisted of: radiotherapy 87 (88%) patients, resection 26 (26%) patients, and systemic chemotherapy 70 (71%) patients, with a median of 1.0 (range 0-8) chemotherapy regimens. The actuarial median survival from diagnosis of BMs is 5 months (95% CI 4-7 months). This single-institution, retrospective study confirms that the prognosis for patients with BMs from TNBC remains poor. This group of patients urgently needs improved therapies. [ABSTRACT FROM AUTHOR]