Whole-genome analysis informs breast cancer response to aromatase inhibition.

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

Splenectomy in the accelerated or blastic phase of chronic myelogenous leukemia: a single-institution, 25-year experience.

BACKGROUND: Patients in the accelerated or blastic phases of chronic myelogenous leukemia (CML) often have painful splenomegaly and secondary thrombocytopenia. We tested the hypothesis that splenectomy can be performed with minimal complications in advanced CML, thereby alleviating pain, reversing thrombocytopenia, and minimizing transfusion requirements. METHODS: We reviewed the records of 53 patients in the accelerated or blastic phases of CML who underwent splenectomy between 1970 and 1995 at the U. T. M. D. Anderson Cancer Center. RESULTS: Twenty-eight patients were in accelerated phase and 25 in blastic phase at the time of splenectomy. The most common indications for splenectomy were symptomatic splenomegaly (median splenic weight, 1000 gm; range, 120 to 6700 gm) or thrombocytopenia (platelet count less than 100,000/microliter) or both. There was 1 death within 30 days of splenectomy. The preoperative platelet count increased 3.72-fold +/- 0.53-fold (mean +/- SEM) by postoperative day 7 (p < 0.001; paired t test). Patients with transfusion-dependent thrombocytopenia had significantly fewer platelet and red blood cell transfusions in the 6 months after splenectomy than in the 6 months before splenectomy (p = 0.016; sign test). CONCLUSIONS: Splenectomy can be performed with minimal morbidity and mortality in advanced CML, thereby relieving symptomatic splenomegaly, reversing thrombocytopenia, and minimizing transfusion requirements.

Impact of extensive intraductal component on recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy.

BACKGROUND: The relationship between an extensive intraductal component (EIC) and recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy has not been clearly defined. METHODS: 133 patients with stage I or II breast cancer who underwent breast conservation therapy between 1978 and 1990 at The University of Texas M. D. Anderson Cancer Center were retrospectively studied. All pathology slides were reviewed to determine tumor size, nuclear grade, extent of intraductal component, number of positive lymph nodes, and histologic margins. EIC was defined as ductal carcinoma in situ (DCIS) occupying 25% or more of the area encompassed by the infiltrating tumor and DCIS present in grossly normal adjacent breast tissue. RESULTS: 110 patients are alive, and 23 have died, with a median follow-up of 7 years; 85 of 133 patients had an intraductal component, but only 18 had an EIC. Locoregional control and disease-free and overall survival were not adversely affected by the presence of an EIC. Five of 133 patients had a locoregional recurrence, but only one had an EIC. CONCLUSIONS: EIC, if negative margins can be achieved, does not adversely affect disease-free or overall survival or local control rates.

Role of conservation therapy for invasive lobular carcinoma of the breast.

BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 5% to 10% of all invasive breast cancers. Although breast conservation therapy using local excision and postoperative irradiation is a standard therapy for early invasive ductal breast cancer, the result of this strategy in ILC is not well documented. We sought to determine the rate of locoregional recurrence after breast conservation therapy in patients with ILC. METHODS: A retrospective review of 74 patients with ILC treated with breast conservation therapy at The University of Texas M. D. Anderson Cancer Center (n = 43) or The John Wayne Cancer Institute (n = 31) between 1977 and 1993 was performed. RESULTS: The median age of patients was 60 years, and median follow-up was 56 months (range 1 to 207 months). Thirty-nine patients had American Joint Committee on Cancer stage I disease, 30 had stage IIa disease, and five had stage IIb disease. All patients underwent surgical resection and postoperative radiation therapy. Twelve patients received postoperative adjuvant chemotherapy, and 27 patients were treated with adjuvant hormonal therapy. The 5-year actuarial locoregional recurrence rate was 9.8%, and the median time to recurrence was 77 months (range 41 to 113 months). Patients with positive or close (< or = 1 mm) surgical margins were at increased risk for local recurrence on univariate analysis (p = 0.034). Of the nine patients with breast recurrence, six underwent salvage therapy with total mastectomy and are disease free at the time of this writing, two patients died of distant disease, and one is alive with local disease at the time of this report. The 5-year disease-specific survival rate was 93.7%. CONCLUSIONS: Breast conservation therapy for ILC achieves locoregional control in the majority of patients. However, long-term follow-up of patients is important because many local recurrences following breast conservation therapy are late events.