Faculty Bibliography

BACKGROUND: At present, there is no consensus regarding how frequently BRCA mutation carriers should be screened for malignancies using breast imaging techniques. An interval malignancy is defined as a malignancy that becomes evident during the period between annual screening mammography scans; the finding of such a malignancy indicates that the malignancy either went undetected by the last breast imaging scan or developed during the interval since that last scan. METHODS: The authors retrospectively reviewed the medical charts of all BRCA mutation carriers who were followed by the genetic counselor at the Columbia-Presbyterian Comprehensive Breast Center (New York, NY) between September 1995 and September 2002. RESULTS: Thirteen BRCA mutation carriers elected to undergo close surveillance and thus were followed at our institution. Three of these 13 patients (23%) did not develop breast carcinoma, 4 (31%) developed breast carcinoma that was detected at the time of annual screening, and 6 (46%) developed palpable interval malignancies in less than 12 months. Among the six patients who developed interval malignancies, the mean time between the last screening mammogram and disease presentation was 5.1 months (range, 2-9 months); the average tumor size in this patient subgroup was 1.7 cm (range, 0.8-3 cm). Two of these six patients had ductal carcinoma in situ, whereas the remaining four had invasive breast carcinoma; three patients had positive lymph nodes at presentation. All six patients who developed interval disease exhibited dense breast tissue on the previous mammogram. Focused breast ultrasonography was able to identify the tumor mass in 3 of 4 patients (75%). CONCLUSIONS: Nearly half of all BRCA-positive women who chose to undergo close surveillance in the current study developed malignant disease less than a year after exhibiting normal findings on screening mammography. Half of these interval malignancies were positive for lymph node involvement. These results suggest that strong consideration should be given to screening BRCA-positive women at more frequent intervals and to using additional imaging techniques, such as breast ultrasonography and/or breast magnetic resonance imaging, as a part of this screening

HYPOTHESIS: The presence of nonsentinel lymph node (NSLN) metastasis after having a positive sentinel lymph node dissection finding is associated with tumor size and stage, the presence of lymphovascular invasion, micrometastasis, and extranodal extension. DESIGN: Retrospective case series. SETTING: University hospital. PATIENTS: Four hundred seven consecutive patients at a single institution who underwent sentinel lymph node dissection as part of breast conservation or mastectomy with biopsy-proved cancer. INTERVENTION: Completion axillary lymph node dissection and definitive therapy. MAIN OUTCOME MEASURES: Sentinel node metastasis, NSLN metastasis, tumor size and stage, lymphovacular invasion, micrometastasis, extronodal extension, histological tumor characteristics, and number of sentinel nodes removed. RESULTS: In a univariate analysis, size of the primary tumor and extranodal extension were associated with having positive NSLN findings. The presence of micrometastasis was associated with negative NSLN findings. When all factors were included in a logistic regression analysis, the significant predictor of NSLN metastasis was extranodal extension (P =.002). Lymphovascular invasion was not associated with positive NSLN findings (P =.11). The number of sentinel nodes removed also had no bearing on the status of the NSLNs (P =.37). CONCLUSIONS: Although primary tumor size and micrometastases correlate with the status of the NSLNs, extranodal extension is the most important independent predictor of NSLN metastasis. These findings may ultimately spare patients a full axillary lymph node dissection. However, pending results of larger clinical trials, full axillary lymph node dissection is still recommended for patients with sentinel lymph node metastases

HYPOTHESIS: Male breast cancer patients have better disease-specific survival than carefully matched female breast cancer patients. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS AND METHODS: Each man in the breast cancer database at Columbia-Presbyterian Medical Center (New York, NY) between the years 1980 and 1998 was matched with a woman. Matching was done based on age and date of diagnosis, stage, and primary histologic findings. MAIN OUTCOME MEASURES: The overall survivals and disease-specific survivals of the male breast cancer group and female breast cancer group were compared. RESULTS: Fifty-three male patients were matched with an equal number of female breast cancer patients. The Kaplan-Meier curves demonstrated that there was no significant difference in overall survival. The 5- and 10-year survivals for women were 0.77 and 0.51, and for men 0.77 and 0.56. When the Kaplan-Meier curves for breast cancer-specific survival were compared, however, there was a significant difference in the 5- and 10-year survivals (P = .05, log-rank test). For women, the 5- and 10-year disease-specific survival was 0.81 and 0.7, respectively, while for men it was 0.9 and 0.9, respectively. In a Cox regression analysis for time to death from breast cancer, stage was the only predictor of death that approached significance (P = .06). CONCLUSIONS: While the overall survivals were equivalent, male breast cancer patients had significantly better disease-specific survivals compared with their female counterparts. Male patients were 4 times more likely to die of other causes than their breast cancer

The management of lobular neoplasia (LN) found on percutaneous core biopsy remains a clinical dilemma. The purpose of this study was to establish guidelines for the management of LN when obtained on percutaneous core needle biopsy. A retrospective review of the Breast Imaging Tissue Sampling Database at New York Presbyterian Hospital-Columbia Comprehensive Breast Center was performed from 1998 to 2000. A total of 1460 percutaneous core breast biopsies were performed using 11- or 14-gauge needles with LN identified in 43 biopsies from 34 patients. Eleven biopsies were ultrasound guided for nonpalpable masses and 32 were stereotactically guided for mammographically detected densities (10) and microcalcifications (22). The 43 LN biopsies were divided into three groups based on additional findings associated with LN on core biopsy: group I (n = 19), LN with invasive cancer or ductal carcinoma in situ (DCIS); group II (n = 11), LN plus a second indication for open surgical biopsy, such as atypical ductal hyperplasia (ADH), radial scar, phyllodes tumor, or intraductal papilloma; and group III (n = 13), LN plus benign fibrocystic changes. In group I, 19 of 19 biopsies (100%) yielded invasive cancer or DCIS on surgical biopsy versus 3 of 11 (27%) for group II, and 1 of 13 (8%) for group III. Outcomes in group III are described as follows: three patients were lost to follow-up, three patients did not undergo surgical biopsy but demonstrated more than 1 year of mammographic stability following core biopsy. Of the remaining seven patients, two had LN and ADH on surgical biopsy (one had a contralateral cancer), one had atypical lobular hyperplasia (with a contralateral cancer), two had LN and benign fibrocystic changes, one had LN and intraductal papilloma, and one had LN and invasive ductal carcinoma (IDC) with DCIS (with a contralateral cancer). These results suggest that surgical biopsy is indicated for patients with LN when found on core biopsy and when the biopsy demonstrates invasive cancer, DCIS, or other indications for surgical biopsy such as ADH, or in the examination of a patient with a synchronous contralateral breast cancer. The diagnosis of LN alone without these indications on percutaneous biopsy may not warrant routine surgical biopsy

Many websites on the Internet offer information to breast cancer patients and are increasingly being used. The authors investigated the potential psychological benefits of Internet use and how it varied as a function of race/ethnicity among 180 white, African American, and Hispanic American breast cancer patients who used the Internet for medical information. Using standardized psychological measures, as measured by the Interpersonal Support Evaluation List (ISEL), Internet use among minorities was associated with greater overall, appraisal, and tangible social support (p's<0.05) but not belonging and self-esteem social support than among whites. No differences were observed for stress, depressive symptoms, loneliness, and coping. Since numerous studies suggest that social support may be related to survival, Internet use for breast health issues may have special clinical relevance to racial/ethnic minority groups

Gene-environment interactions are hypothesized to be major contributors to susceptibility to environmental carcinogens and interindividual variability in cancer risk. We present findings on associations between genetic susceptibility due to inherited polymorphisms of the Phase II detoxification enzyme sulfotransferase 1A1 (SULT1A1), breast cancer risk, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts. A hospital based case-control study was conducted at the New York-Presbyterian Medical Center (NYPMC). The study utilized two control groups: one comprised of women with benign breast disease (BBD) and the other comprised of women visiting NYPMC for routine gynecologic checkups (healthy controls). Blood samples were collected from cases and controls; and breast tissue from pathology blocks was collected from cases (tumor and non-tumor tissue) and BBD controls (benign tissue). PAH-DNA adduct levels were measured by immunohistochemistry in breast tissue samples, and the SULT1A1 (Arg/His) polymorphism at codon 213 was determined by PCR RFLP analyses using DNA from white blood cells. Increasing number of His alleles was modestly associated with breast cancer case-control status, when cases were compared to healthy controls (p for trend = 0.08), when cases were compared to BBD controls (p for trend = 0.08) and when cases were compared to both control groups combined (p for trend = 0.07). Contrary to our hypothesis PAH-DNA adduct levels in breast tissue were not associated with SULT1A1 genotype. Our findings are consistent with a prior report that the Arg/His polymorphism in SULT1A1 is associated with breast cancer risk

Systemic diseases rarely present with manifestations in the breast. Disorders such as sarcoidosis and pyoderma gangrenosum have been described to produce signs and symptoms in the breast. Peripheral eosinophilia is a systemic disease associated with a finite group of conditions including asthma, allergic or atopic disease, collagen vascular disease, and parasitic infection. In addition it has been described in association with several malignancies. A 50-year-old woman with a history of asthma and significant eosinophilia presented with an enlarging breast mass. Complete excision of the mass revealed eosinophilic mastitis. Two years later the patient again presented with a large mass in the same breast. Repeat excision demonstrated the same pathology. The clinical significance of this lesion is important because it presents as an enlarging, painless, dominant mass. Excision is necessary for management and to conclusively rule out malignancy. Its recurrence despite excision to negative margins, however, may indicate that control of the eosinophilia--and possibly the underlying disorder--is important to prevent further recurrence

HYPOTHESIS: The changes reported with pulse oximetry after the injection of isosulfan blue for sentinel lymph node identification in patients with breast cancer are consistent and predictable. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS AND METHODS: The complete anesthesia records of 92 patients who underwent sentinel lymph node biopsy with intraparenchymal injection of isosulfan blue were reviewed. The study extended from January 1999 to February 2000. The operations were all performed after the patient received general anesthesia. We injected 5 mL of isosulfan blue into the breast tissue surrounding the tumor. The data reviewed included preinjection pulse oximeter saturation readings and postinjection values continuing until the readings returned to baseline levels in the postanesthesia care unit. MAIN OUTCOME MEASURES: Changes in oxygen saturation readings with the pulse oximeter before and after injection of isosulfan blue. RESULTS: Isosulfan blue injection interfered with pulse oximeter measurements for a substantial time-as much as 195 minutes. The mean time to the maximum change in the pulse oximeter reading was 35 minutes. The median decrease in oxygen saturation was 5%. The maximum decrease in the pulse oximeter reading was 11%. CONCLUSIONS: Although the changes in pulse oximeter readings can be substantial, their course appears to be predictable, and therefore in most otherwise healthy patients with normal pulmonary function, invasive monitoring is not necessary

A 90-year-old woman who underwent a left modified radical mastectomy 40 years ago with no further adjuvant treatment presented with a left chest wall mass at the suture line. A biopsy of the mass confirmed that it was invasive ductal carcinoma of the breast. After a negative metastatic work-up, the patient underwent a local resection of the chest wall mass with clear margins. We present here the longest documented delayed recurrence after modified radical mastectomy reported in the literature

We review our studies on the role of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in breast cancer. Additionally we report on analyses of the reliability of the scoring procedures used with immunohistochemical assay for PAH-DNA adducts and of potential bias arising from the use of benign breast disease (BBD) controls. We conducted a case-control study utilizing two control groups: BBD controls who donated tissue and blood samples, and healthy controls who donated blood samples. In comparisons of tumor tissue from cases and benign tissue from BBD controls, increasing adduct levels were significantly associated with case-control status [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.18-4.92], whereas in comparisons of nontumor tissue from cases and benign tissue from BBD controls the association was nonsignificant (OR = 1.97, 95% CI 0.94-4.17). We also show among cases, but not among BBD controls, that the GSTM1 null genotype is associated with increased adduct levels in breast tissue. Our reliability study found the scoring procedures used with the immunohistochemical assay to have high reliability, 0.93 in nontumor, 0.82 in tumor, and 0.74 in benign tissues. However, we found that the technician significantly contributed to the total variability of a series of data. Finally, we did not find a consistent bias to the null associated with the use of BBD controls; however, BBD controls may overestimate the prevalence of family history of breast cancer compared to that of healthy controls (18% vs.14%). We hypothesize that the higher prevalence results from a referral bias and discuss how this may influence our results