Predictors of breast cancer development in a high-risk population.

BACKGROUND: The purpose of this study was to investigate the strongest predictors of breast cancer in a high-risk population and to increase our understanding of the possible interactions between risk factors. METHODS: The Women At Risk High-Risk Registry provided the study population. The variables of interest included age at enrollment, presence of lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, family history of breast cancer, body mass index, and Gail scores (5-year high-risk > or =1.7%). Univariate and multivariate analyses were conducted with the Cox proportional hazards regression model and years of follow-up evaluation as the time scale. RESULTS: Out of 1553 high-risk women, 79 (5%) developed breast cancer during a median follow-up period of 5 years. Results from the multivariate Cox model demonstrated that FHBC (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.05-2.97), ADH (HR = 1.90; 95% CI, 1.16-3.13), LCIS (HR = 1.71; 95% CI, .99-2.95), and a body mass index > or =30 (HR = 2.22; 95% CI, 1.14-4.35) were statistically significant predictors of breast cancer within this high-risk population. CONCLUSIONS: These results support current literature showing the synergistic increase in risk for patients with ADH, LCIS, and a positive family history of breast cancer. Obesity was also a strong predictor of breast cancer risk, which suggests that there may be a potentiating effect of obesity on other risk factors. Obesity may represent a modifiable risk factor, providing women with an opportunity to reduce their risk with lifestyle modification. Women with a strong family history of breast cancer or a diagnosis of ADH or LCIS may benefit most from risk-reduction strategies, chemoprevention, and surveillance.

Prediction of breast cancer using volatile biomarkers in the breath.

We evaluated a breath test for volatile organic compounds (VOCs) as a predictor of breast cancer. Breath VOCs were assayed in 51 asymptomatic women with abnormal mammograms and biopsy-proven breast cancer, and 42 age-matched healthy women. A fuzzy logic model predicted breast cancer with accuracy superior to previously reported findings. Following random assignment to a training set (64) or a prediction set (29), a model was constructed in the training set employing five breath VOCs that predicted breast cancer in the prediction set with 93.8% sensitivity and 84.6% specificity. The same model predicted no breast cancer in 16/50 (32.0%) women with abnormal mammograms and no cancer on biopsy. A two-minute breath test could potentially provide a safe, accurate and painless screening test for breast cancer, but prospective validation studies are required.

The value of clinical characteristics and breast-imaging studies in predicting a histopathologic diagnosis of cancer or high-risk lesion in patients with spontaneous nipple discharge.

BACKGROUND: The purpose of this study was to determine the utility of breast-imaging studies in identifying cancer and high-risk lesions among patients with spontaneous, single-duct, nipple discharge (SSND). METHODS: The medical records of 168 cases with SSND treated with duct excision between June 1998 and May 2004 were reviewed. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mammogram, ultrasound, and ductogram in predicting high-risk lesions and cancer were calculated. RESULTS: The sensitivity of mammography was 10%, the specificity 94%, the NPV 88%, and the PPV 18%. Ultrasonography had a sensitivity of 36%, specificity of 68%, PPV of 14%, and NPV of 89%. Ductography had a sensitivity of 75%, specificity of 49%, and NPV and PPV of 93% and 18%, respectively. CONCLUSIONS: Conventional imaging studies do not accurately identify cancer or high-risk lesions in patients with SSND. All patients with SSND should be offered duct excision.

Allergic reactions to isosulfan blue in sentinel lymph node mapping.

BACKGROUND: Sentinel lymph node (SLN) biopsy is often used in the assessment of lymph node status in melanoma and early stage breast cancer. With the rapidly increasing use of the technique, we can now better characterize and assess the rate of adverse reactions to the dye. METHODS: A retrospective review of all patients undergoing SLN mapping at the Columbia-Presbyterian Breast Center were identified from June 2000 to July 2002. All patients who experienced allergic reactions were documented and records examined. RESULTS: In total, three out of 351 patients had allergic complications from the procedure. All three patients developed "blue hives" after injection with isosulfan blue. The incidence at our Breast Center was 0.9%. All were treated with intravenous corticosteroids and diphenhydramine and recovered within twenty-four hours. CONCLUSIONS: The increasing utilization of the sentinel lymph node technique will make these complications more common. A high index of suspicion and appropriate clinical management are recommended to minimize the potential morbidity of these reactions.

Men with breast cancer have better disease-specific survival than women.

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.

Predictors of nonsentinel node metastasis in patients with breast cancer after sentinel node metastasis.

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.

The development of interval breast malignancies in patients with BRCA mutations.

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.

Pure mucinous carcinoma of the breast.

BACKGROUND: The lack of a standard definition of "pure" mucinous carcinoma of the breast has made it difficult to compare data from different studies. This study used the most stringent criteria to define parameters for truly pure lesions. METHODS: Sixty-five patients were identified. The database was used to evaluate patients' demographics, tumor characteristics, and outcomes. Survival curves and predictors of survival were analyzed. RESULTS: The mean age of presentation was 67 years. The majority (96%) of patients presented with early-stage disease. The 5- and 10-year overall survival rates were 93.6% and 72.8%, respectively. The number of involved axillary lymph nodes was the only significant predictor of death (P = 0.02). CONCLUSIONS: Pure mucinous carcinoma of the breast has a favorable prognosis. Tumor size does not appear to impact survival, perhaps because the volume of mucin overestimates tumor burden. The number of involved axillary lymph nodes was the only significant predictor of death from disease.

Interpectoral nodes as the initial site of recurrence in breast cancer.

HYPOTHESIS: Interpectoral nodes can be the initial site of recurrent breast cancer. DESIGN: Retrospective review. SETTING: Comprehensive breast center, located in a university-based tertiary care center. PATIENTS: All patients undergoing operations for breast cancer at our breast center from 1995 to 2002 were reviewed. MAIN OUTCOME MEASURES: Patients with interpectoral node recurrence as the initial site of recurrent breast cancer were identified. RESULTS: During the 8-year period, 4097 patients underwent surgical management for breast cancer. During this time, 4 patients (0.1%) had recurrence at the interpectoral nodes. Three of the 4 patients were node-negative at the original operation. All lesions were mammographically occult. Preoperative needle biopsy was effective in the confirmation of malignancy. All 4 underwent excision without complications. CONCLUSIONS: Recurrence at the interpectoral nodes can be the initial site of surgical failure. These nodes may represent the site of primary drainage in a percentage of patients. The sentinel node identification technique, therefore, should diminish the number of patients affected by recurrence at this site. In patients with a palpable mass in the infraclavicular location, however, a high index of suspicion should be maintained. Workup should include additional breast imaging and needle biopsy prior to operation.

Survival and recurrence after breast cancer in BRCA1/2 mutation carriers.

BACKGROUND: Genetic mutation is responsible for approximately 10% of breast cancers. The purpose of this study was to compare breast cancer survival and recurrence rates between BRCA1/2 mutation carriers and noncarriers. METHODS: Using the Columbia Presbyterian breast cancer database, we collected the tissue blocks of all patients younger than 65 years of age and of Jewish descent. The patients were contacted and the data updated. DNA was extracted from the tissue blocks and tested for the common mutations. The results of the genetic mutation and updated database were anonymized and merged. The survival and recurrence rates were compared between mutation carriers and noncarriers. RESULTS: A total of 739 breast cancer cases in 715 patients were identified. We were able to test 487 patients. We identified 30 BRCA1 and 21 BRCA2 mutation carriers, for an incidence of 10.36%. The median follow-up for the patients tested was 50 months. BRCA1 patients more frequently had estrogen- and progesterone-negative tumors and had a higher incidence of positive nodes. BRCA1 patients received chemotherapy more frequently. The incidence of in situ disease was similar for mutation and non-mutation carriers. BRCA1/2 mutation carriers had a higher incidence of bilateral disease. There was no difference in 5- or 10-year overall and breast cancer-specific survival between mutation and non-mutation carriers. CONCLUSIONS: Breast cancer patients with BRCA1/2 mutations have a similar outcome as non-mutation carriers.

A 40-year delayed locoregional recurrence of breast carcinoma following mastectomy.

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.

Pulse oximeter changes with sentinel lymph node biopsy in breast cancer.

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.

Volatile markers of breast cancer in the breath.

Breast cancer is accompanied by increased oxidative stress and induction of polymorphic cytochrome P-450 mixed oxidase enzymes (CYP). Both processes affect the abundance of volatile organic compounds (VOCs) in the breath because oxidative stress causes lipid peroxidation of polyunsaturated fatty acids in membranes, producing alkanes and methylalkanes which are catabolized by CYP. We performed a pilot study of breath VOCs, a potential new marker of disease in women with breast cancer. This was a combined case-control and cross-sectional study of women with abnormal mammograms scheduled for a breast biopsy. Breath samples were analyzed by gas chromatography and mass spectroscopy in order to determine the breath methylated alkane contour (BMAC), a three-dimensional display of the alveolar gradients (abundance in breath minus abundance in room air) of C4-C20 alkanes and monomethylated alkanes. BMACs in women with and without breast cancer were compared using forward stepwise discriminant analysis. Two hundred one breath samples were obtained from women with abnormal mammograms and biopsies read by two pathologists. There were 51 cases of breast cancer in 198 concordant biopsies. The breath test distinguished between women with breast cancer and healthy volunteers with a sensitivity of 94.1% (48/51) and a specificity of 73.8% (31/42) (cross-validated sensitivity 88.2% (45/51), specificity 73.8% (31/42)). Compared to women with abnormal mammograms and no cancer on biopsy, the breath test identified breast cancer with a sensitivity of 62.7% (32/51) and a specificity of 84.0% (42/50) (cross-validated sensitivity of 60.8% (31/51), specificity of 82.0% (41/50)). The negative predictive value (NPV) of a screening breath test for breast cancer was superior to a screening mammogram (99.93% versus 99.89%); the positive predictive value (PPV) of a screening mammogram was superior to a screening breath test (4.63% versus 1.29%). A breath test for markers of oxidative stress accurately identified women with breast cancer, with an NPV superior to a screening mammogram. This breath test could potentially be employed as a primary screen for breast cancer. Confirmatory studies in larger groups are required.

Racial/ethnic differences and potential psychological benefits in use of the internet by women with breast cancer.

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.

The management of lobular neoplasia identified on percutaneous core breast biopsy.

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.

Internet use and social support in women with breast cancer.

Many Web sites offer information to breast cancer patients, who are increasingly using these sites. The authors investigated the potential psychological benefits of Internet use for medical information by breast cancer patients. Of the 251 women approached, 188 were successfully interviewed (74.9%). Forty-two percent used the Internet for medical information related to breast health issues and did so for an average of 0.80 hr per week. The Interpersonal Support Evaluation List and the UCLA Loneliness Scale, with results controlled for covariates, showed that Internet use for breast health issues was associated with greater social support and less loneliness than Internet use for other purposes or nonuse. Breast cancer patients may obtain these psychological benefits with only a minimal weekly time commitment.