Faculty Bibliography

Whether postmenopausal hormone-replacement therapy (HRT) increases the risk of breast cancer remains controversial, despite numerous epidemiological studies. We approached the question from a biochemical rather than an epidemiological direction - we hypothesized that if estrogen administration increases the risk of breast cancer, it should also alter a known estrogen biomarker of risk towards what has been observed in patients who already have breast cancer. The specific biomarker we studied was the ratio of the urinary excretion of two principal estradiol metabolites, 2-hydroxyestrone and 16 alpha-hydroxyestrone, which is markedly decreased in women with breast cancer and women with familial risk for breast cancer. We studied 34 healthy postmenopausal women not on HRT and 19 women on HRT (Premarin 0.625 mg daily plus Provera, 2.5 mg daily, in women with a uterus and Premarin alone in women without a uterus); treatment duration ranged from 3 months to 15 years. We also studied four women with recently diagnosed, untreated breast cancer. The women with breast cancer showed a significantly lower 2-hydroxyestrone to 16 alpha-hydroxyestrone ratio than control women on HRT (1.35 +/- 0.13 vs. 2.71 +/- 0.84; p < 0.0001). There was no significant difference in the metabolite ratio between healthy women on HRT and women not on HRT (2.82 +/- 0.92 vs. 2.71 +/- 0.84). There was no significant difference between women receiving Premarin alone and women receiving Premarin plus Provera (2.46 +/- 0.84 vs. 3.13 +/- 0.90), and neither differed significantly from women not on HRT (2.71 +/- 0.84). The finding that the ratio of women on HRT was not decreased to or toward the ratio in women with breast cancer can be interpreted, we believe, as a suggestive item of biochemical evidence that HRT is not a risk for breast cancer

Multicentric or multifocal breast cancer is considered as one of the limitations for sentinel lymph node (SLN) localization. We did a retrospective analysis to evaluate the success rate, sensitivity, accuracy, and negative predictive values of SLN localization in multicentric or multifocal breast lesions. METHODS: Fifty-nine patients with multifocal or multicentric breast lesions proven by either fine-needle aspiration (19/59), core biopsy (39/59), or lumpectomy (8/59) underwent SLN localization. Of these patients, 46 had SLN localization by both radiocolloid and blue dye, and 13 had SLN localization by radiocolloid alone. Approximately 10 MBq (99m)Tc-labeled unfiltered sulfur colloid in 0.3-0.4 mL were injected intradermally over the 1 or 2 breast tumor locations 2-4 h before surgery. During surgery, vital blue dye was injected intraparenchymally in 4-6 places around the tumor. All lymph nodes with counts of >10 times that of the background counts, whether or not blue dye positive, and all blue dye-positive lymph nodes, whether or not radiocolloid positive, were excised and labeled accordingly. All lymph nodes underwent frozen sectioning and were examined by hematoxylin and eosin and immunohistologic (cytokeratin) staining. RESULTS: Of the 59 patients, 48 had axillary lymph node dissection irrespective of the results of pathologic examination of the SLN. The success rate, sensitivity, negative predictive value, and accuracy were 93%, 100%, 100%, and 100% using the radiocolloid probe, 87%, 100%, 100%, and 100% using blue dye, and 93.5%, 100%, 100%, and 100% using combined methods, respectively. Concordance between blue dye and radiocolloid was 91% (the incidence of the number of sentinel nodes detected was 37.5%, 30.3%, 10.7%, and 21.4% for 1, 2, 3, and 4 or more lymph nodes, respectively). Metastatic lymph node involvement was found in 39.5% of patients. CONCLUSION: The sentinel node localization approach showed a high negative predictive value in breast cancer patients with multifocal or multicentric lesions, contrary to the common belief of significant false-negative results in these patients

BACKGROUND: Although stereotaxic fine-needle aspiration biopsy or core biopsy (14-gauge) have proven to be accurate techniques for the evaluation of mammographically detected microcalcification, the development of the Mammotome Biopsy System (Biopsys Medical, Inc., Irvine, CA) has led many medical centers to use this vacuum-assisted device for the sampling of microcalcification. METHODS: One hundred forty-two women underwent 160 stereotaxic Mammotome core biopsies of mammographic calcification over a 1-year period. The stereotaxic procedure was performed by radiologists using the Mammotome Biopsy System. Microcalcification was evident on specimen radiographs and microscopic slides in 99% of the cases. Excisional biopsy was recommended for diagnoses of atypia or carcinoma. Patients with benign diagnoses underwent mammographic followup. RESULTS: One hundred thirty-two benign, 12 atypical, and 15 adenocarcinoma diagnoses (comprising 1 lobular adenocarcinoma in situ [LCIS], 1 invasive ductal adenocarcinoma [IDC], and 13 intraductal adenocarcinomas [DCIS]: 10 comedo, 1 cribriform, 2 mixed cribriform and micropapillary) were rendered. Surgical excision in eight patients with atypia on Mammotome biopsy (two refused surgery, two were lost to followup) showed ductal hyperplasia in three, atypical ductal hyperplasia (ADH) in three and DCIS (low grade, solid) in two patients. Surgical excisions in 14 patients diagnosed with carcinoma (1 patient lost to followup) showed ADH in 3, ADH and LCIS in 1, residual DCIS in 8, IDC in 1, and microinvasive carcinoma in 1 patient. CONCLUSIONS: A diagnosis of atypia on Mammotome biopsy warranted excision of the atypical area, yet the underestimation rate for the presence of carcinoma remained low. The likelihood of an invasive component at excision was low for microcalcification diagnosed as DCIS on Mammotome biopsy. Mammotome biopsy proved to be an accurate technique for the sampling and diagnosis of mammary microcalcification