Long-term outcome of (neo)adjuvant zoledronic acid therapy in locally advanced breast cancer.

PURPOSE: The role of zoledronic acid (ZOL), a bone-targeted bisphosphonate, in the treatment of patients with breast cancer remains an active area of study. Here, we report the long-term outcomes of a randomized placebo-controlled phase II clinical trial in which ZOL treatment was added to neoadjuvant chemotherapy in women with locally advanced breast cancer. METHODS: 120 women with clinical stage II-III (≥ T2 and/or ≥ N1) newly diagnosed breast cancer were randomized to receive either 4 mg intravenous ZOL every 3 weeks for 1 year (17 total doses) beginning with the first dose of neoadjuvant chemotherapy, or chemotherapy alone. Clinical endpoints included time to recurrence (TTR), time to bone recurrence (TTBR), time to non-bone recurrence (TTNBR), breast cancer survival (BCS) and overall survival (OS). RESULTS: With a median follow-up interval of 14.4 years, there were no significant differences in any of the clinical endpoints studied between the control and ZOL groups in the overall study population. However, ER+/HER2- patients younger than age 45 who were treated with ZOL had significantly worse TTR and TTNBR with a trend towards worse TTBR, BCS and OS (TTR: P = 0.024, HR 6.05 [1.26-29.1]; TTNBR: P = 0.026, HR 6.94 [1.26-38.1]; TTBR: P = 0.054, HR 6.01 [0.97-37.1]; BCS: P = 0.138, HR 4.43 [0.62-31.7]; OS: P = 0.138, HR 4.43 [0.62-31.7]). These differences were not seen in older ER+/HER2- patients or triple-negative patients of any age. CONCLUSION: Addition of ZOL to neoadjuvant therapy did not significantly affect clinical outcomes in the overall study population but was associated with increased extra-skeletal recurrence and a trend towards worse survival in ER+/HER2- patients younger than age 45. These findings suggest caution when using zoledronic acid in young, premenopausal women with locally advanced breast cancer and warrant further investigation. Clinical Trial Registration Number NCT00242203, Date of Registration: 10/17/2005.

US breast cancer mortality trends in young women according to race.

BACKGROUND: Young age at diagnosis has a negative prognostic impact on outcome in patients with breast cancer (BC). In the current study, the authors sought to determine whether there is a differential effect of race and examined mortality trends according to race and age. METHODS: The Surveillance, Epidemiology, and End Results program was used to identify women aged <50 years with invasive BC diagnosed between 1990 and 2009. Multivariate regression analyses were performed to determine the risk-adjusted likelihood of survival for white and black patients. Annual hazards of BC death according to race and calendar period and adjusted relative hazards of death for white and black women stratified by age were computed. RESULTS: A total of 162,976 women were identified, 126,573 of whom were white, 20,405 of whom were black, and 15,998 of whom were of other races. At a median follow-up of 85 months, the 5-year disease specific survival rates were 90.1% for white patients and 79.3% for black patients. Annual hazards of death in white patients decreased by 26% at 5 years after diagnosis in contrast to the hazards in black patients, which decreased by only 19%. With 1990 as the referent year, the adjusted relative hazards of death in women aged <40 years in 2005 were 0.55 (95% confidence interval [95% CI], 0.46-0.66) and 0.68 (95% CI, 0.49-0.93), respectively, for white and black women. In women aged 40 to 49 years, adjusted hazards of death were 0.53 (95% CI, 0.47-0.60) and 0.78 (95% CI, 0.61-0.99), respectively, for white and black women. CONCLUSIONS: Among young women diagnosed with BC, black patients have a worse outcome compared with white patients. Mortality declines have been observed over time in both groups, although more rapid gains have been reported to occur in white women. Emphasis should be placed on improving outcomes for young patients with BC.

Disease recurrence in sentinel node-positive breast cancer patients forgoing axillary lymph node dissection.

BACKGROUND: Clinically node-negative breast cancer patients usually undergo sentinel lymph node (SLN) biopsy. When metastasis is identified, completion axillary lymph node dissection (CALND) is recommended. Newer data suggest that CALND may be omitted in some women as it does not improve local control or survival. METHODS: Women with a positive SLN diagnosed between 1999 and 2010 were included in this review and were stratified according to whether they did or did not undergo CALND. Primary endpoints included recurrence and breast cancer-specific mortality. Differences between the groups and in time to recurrence were compared and summarized. RESULTS: Overall, 276 women were included: 206 (79 %) women who underwent CALND (group 1) and 70 (21 %) women in whom CALND was omitted (group 2). Group 1 patients were younger, had more SLN disease, and received more chemotherapy (P < 0.05 for each). The groups did not vary by tumor characteristics (P > 0.05 for each). Median follow-up was 69 (range 6-147) and 73 (range 15-134) months for groups 1 and 2, respectively. Five (2 %) women in group 1 and three (4 %) women in group 2 died of breast cancer (P = 0.39). Local-regional or distant recurrence occurred in 20 (10 %) group 1 patients and in 10 (14 %) group 2 patients (P = 0.39). On multivariate analysis, only estrogen receptor negativity and lymphovascular invasion predicted for recurrence. CONCLUSIONS: Omission of CALND in women with SLN disease does not significantly impact in-breast, nodal, or distant recurrence or mortality. Longer-term follow-up is needed to verify that this remains true with time.

Neoadjuvant chemotherapy is associated with improved survival compared with adjuvant chemotherapy in patients with triple-negative breast cancer only after complete pathologic response.

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is known to be chemosensitive. In patients with TNBC, we sought to compare survival outcomes between patients receiving neoadjuvant chemotherapy, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy. METHODS: We performed a retrospective chart review and identified 385 patients with stage I-III TNBC who were treated with neoadjuvant or adjuvant chemotherapy between 2000 and 2008. Patients were divided according to receipt of neoadjuvant chemotherapy with pCR, neoadjuvant chemotherapy without pCR, and adjuvant chemotherapy. Data were compared using Fisher's exact test and analysis of variance (ANOVA). Kaplan-Meier curves were generated. RESULTS: Of 385 patients, 151 (39%) received neoadjuvant chemotherapy and 234 (61%) received adjuvant chemotherapy. Twenty-six (17%) of those patients receiving neoadjuvant chemotherapy had pCR. After controlling for covariates associated with survival in unadjusted tests, patients undergoing neoadjuvant chemotherapy with residual tumor had significantly worse survival compared with patients receiving adjuvant therapy [hazard ratio (HR) = 0.51, P = 0.007] and a trend towards worse survival compared with patients receiving neoadjuvant therapy with pCR (HR = 0.19, P = 0.10). CONCLUSIONS: Although previous clinical trials have not demonstrated a survival difference between patients receiving neoadjuvant versus adjuvant chemotherapy for breast cancer, our study suggests an overall survival benefit in patients with pCR following neoadjuvant chemotherapy compared with patients receiving adjuvant therapy. It is clear that a prospective study needs to be carried out to better elucidate the timing of chemotherapy in patients with TNBC.

Positive margin rates following breast-conserving surgery for stage I-III breast cancer: palpable versus nonpalpable tumors.

BACKGROUND: Margin status is a significant risk factor for local recurrence. We sought to examine whether the method of tumor localization predicted the margin status and the need for re-excision for both nonpalpable and palpable breast cancer. METHODS: We identified 358 consecutive breast cancer patients who were treated with breast-conserving therapy (BCT) from 1999 to 2006. Data included patient and tumor characteristics, method of localization (needle versus palpation), and pathologic outcomes. Descriptive statistics were used for data summary and data were compared using χ(2). RESULTS: Of 358 patients undergoing BCT, 234 (65%) underwent needle localization for a nonpalpable tumor and 124 (35%) underwent a palpation-guided procedure. Patients undergoing palpation-guided procedures were younger and had larger tumors at a more advanced pathologic stage of disease than those undergoing needle localization procedures (P < 0.05 for each). Patient race, tumor grade, presence of lymphovascular invasion, biomarker profile, and nodal status were not significantly different between the two groups (P > 0.05). Overall, 137 patients (38%) had one or more positive margins: 90 of 234 (38%) who had a needle localization procedure and 47 of 124 (38%) who had a palpation-guided procedure (P > 0.05). The number of margins affected did not differ significantly between the two groups. CONCLUSION: Although patients with palpable breast cancer had larger tumors than those with nonpalpable breast cancer, the incidence and number of positive margins was similar to those who had needle localization for nonpalpable tumors. Improved methods of localization are needed to reduce the rate of positive margins and the need for re-excision.

Compromised margins following mastectomy for stage I-III invasive breast cancer.

BACKGROUND: We investigated factors associated with positive margins following mastectomy and the impact on outcomes. METHODS: We identified 240 patients with stage I-III invasive breast cancer who underwent mastectomy from 1999 to 2009. Data included patient and tumor characteristics, pathologic margin assessment, and outcomes. Margin positivity was defined as the presence of in situ or invasive malignancy at any margin. Descriptive statistics were used for data summary and were compared using χ(2). RESULTS: Of the 240 patients, 132 (55%) had a simple mastectomy with sentinel lymph node biopsy and 108 (45%) had a modified radical mastectomy. Overall, 21 patients (9%) had positive margins, including 12 (57%) with one positive margin, 3 (14%) with two positive margins, and 6 (29%) with three or more positive margins. The most commonly affected margin was the deep margin (48% of patients). Eight of the 21 patients (38%) received adjuvant chest wall irradiation. There were no differences between patients who had a positive margin and those who did not with respect to patient age, race, percentage of in situ component, tumor size, tumor grade, lymphovascular invasion, or immunostain profile (P > 0.05 for all). None of the patients with positive margins experienced a local recurrence. CONCLUSIONS: Positive margins following mastectomy occurred in nearly 10% of our patients. No specific patient or tumor characteristics predicted a risk for having a positive margin. Despite the finding that only approximately 40% of patients received adjuvant radiation in the setting of a positive margin, no local recurrences have been observed.

Impact of consensus guidelines for breast-conserving surgery in patients with ductal carcinoma in situ.

BACKGROUND: Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re-excision practices. AIMS: To evaluate the impact of this consensus guideline on our institutional practices. METHODS: We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectively-maintained institutional database. A retrospective chart review was performed to determine margin status and re-excision rates during the 2 years before and the 2 years after the guideline was published in order to determine the effect on our re-excision rates. Close margins were defined as <2 mm. RESULTS: In the 2 years before the consensus guideline was published, 184 patients with DCIS underwent BCS. Twenty-six patients had positive margins and 24 underwent re-excision, including three who had completion mastectomy. Of the remaining 159 patients, 76 had ≥2 mm (negative) margins. The remaining 82 patients had close margins and 48 of these patients (58.5%) underwent re-excision, including one who had a completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 30.4% prior to the guideline. In the 2 years after the consensus guideline was published, 192 patients with DCIS underwent initial BCS. Twenty-four patients had positive margins and 22 underwent re-excision, including three who had completion mastectomy. Of the remaining 168 patients, 95 patients had ≥2 mm (negative) margins. The remaining 73 patients had close margins and 45 of those patients (61.6%) underwent re-excision, including six who had completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 26.8% after the guideline. CONCLUSIONS: Our institution's re-excision rate did not change significantly during the 2 years before and after the publication of the consensus guideline on adequate margins for patients undergoing BCT for DCIS. Our overall re-excision rate decreased slightly. However, of the patients who had close margins, a larger proportion underwent re-excision after the guideline was published. The guideline publication appears to have affected our institutional practices slightly, but not dramatically as many of our surgeons' practices were comparable to the guideline recommendations prior to 2016. We continue to use clinical judgment based on patient and tumor characteristics in deciding which patients will benefit from margin re-excision.

Correlates of fear of cancer recurrence in women with ductal carcinoma in situ and early invasive breast cancer.

Fear of cancer recurrence (FCR) is a common and persistent concern among breast cancer survivors. Little is known about factors associated with FCR in women with ductal carcinoma in situ (DCIS) or early invasive breast cancer (EIBC). Women with first primary DCIS, or stages I-IIA breast cancer were prospectively enrolled in a quality-of-life study and completed interviews at 4-6 weeks, 6 months, and 2 years after definitive surgical treatment. In three stepwise multivariable linear regression models, including both time-independent and time-varying variables measured at each respective interview, we identified independent correlates of mean FCR scores (range 1-6) using four items from the Concern About Recurrence Scale (CARS) at 2-year follow-up. Of 506 disease-free patients at 2-year follow-up (mean [SD] age, 58 [10] years; 81% White; 34% DCIS), the average FCR score of 2.0 was low. However, 145 (29%) reported moderate-to-high levels of FCR (scores 3.0-6.0). All three models showed that younger age, stage IIA breast cancer (vs. DCIS), lower social support, and elevated anxiety were consistently associated with higher FCR at 2-year follow-up (each P < 0.05; final models R (2) = 0.25-0.32). DCIS patients reported lower FCR than stage IIA patients (each P ≤ 0.01) but had similar FCR as stage I patients. Although mean FCR was low, 29% of DCIS and EIBC survivors reported moderate-to-high levels of FCR at 2-year follow-up. Management of anxiety, provision of social support, and patient education may help reduce FCR among DCIS and EIBC survivors, especially among younger survivors.

Are we overtreating papillomas diagnosed on core needle biopsy?

BACKGROUND: Breast papillomas often are diagnosed with core needle biopsy (CNB). Most studies support excision for atypical papillomas, because as many as one half will be upgraded to malignancy on final pathology. The literature is less clear on the management of papillomas without atypia on CNB. Our goal was to determine factors associated with pathology upgrade on excision. METHODS: Our pathology database was searched for breast papillomas diagnosed by CNB during the past 10 years. We identified 277 charts and excluded lesions associated with atypia or malignancy on CNB. Two groups were identified: papillomas that were surgically excised (group 1) and those that were not (group 2). Charts were reviewed for the subsequent diagnosis of cancer or high-risk lesions. Appropriate statistical tests were used to analyze the data. RESULTS: A total of 193 papillomas were identified. Eighty-two lesions were excised (42%). Caucasian women were more likely to undergo excision (p = 0.03). Twelve percent of excised lesions were upgraded to malignancy. Increasing age was a predictor of upgrading, but this was not significant. Clinical presentation, lesion location, biopsy technique, and breast cancer history were not associated with pathology upgrade. Two lesions in group 2 ultimately required excision due to enlargement, and both were upgraded to malignancy. CONCLUSIONS: Twenty-four percent of papillomas diagnosed on CNB have upgraded pathology on excision--half to malignancy. All of the cancers diagnosed were stage 0 or I. For patients in whom excision was not performed, 2 of 111 papillomas were later excised and upgraded to malignancy.

Breast cancer in elderly women (≥ 80 years): variation in standard of care?

OBJECTIVE: The study aim was to investigate the methods of breast cancer diagnosis and treatment for women at advanced ages. METHODS: We identified 134 patients ≥ 80 years old treated for breast cancer. Data included patient and tumor characteristics, treatment, and outcomes. RESULTS: Of 134 women ≥ 80 years old, 146 breast cancers were diagnosed. Sixty-five (45%) were detected by mammography. Surgical therapy included partial mastectomy in 50% and mastectomy in 50%. Although 12 (9%) women had no axillary staging, 22 (16%) underwent axillary lymph node dissection for node-negative disease. Of 73 patients undergoing partial mastectomy, 34 (47%) received adjuvant radiation. Of 113 cancers with known estrogen receptor (ER) status, 83% were ER positive; 95% received endocrine therapy. Fourteen (10%) received adjuvant chemotherapy. Eleven (8%) were Her-2 neu-amplified; one patient received adjuvant trastuzumab. At follow-up, 87 (65%) patients were alive without evidence of disease, while 6 (4%) died of breast cancer. CONCLUSIONS: Breast cancer in women ≥ 80 years is more likely to be early-stage with favorable tumor biology. While most women eligible for anti-estrogen therapy received it, adjuvant radiation, chemotherapy, and/or trastuzumab were utilized infrequently. Despite these variations, older women with breast cancer are unlikely to suffer breast cancer-related mortality.

Impact of multiple caregiving roles on elevated depressed mood in early-stage breast cancer patients and same-age controls.

The effect of caregiving roles on risk of elevated depressed mood over 12 months was examined in early-stage (0-IIA) breast cancer patients and same-aged women without breast cancer. Women were interviewed 4-6 weeks, 6 months, and 12 months following definitive surgical treatment (patients) or routine screening mammogram (controls). The Center for Epidemiologic Studies-Depression Scale was administered at each interview and dichotomized for analysis (<16 [little/no depressed mood] vs. >or=16 [elevated depressed mood]). Participants were categorized as having no caregiving responsibilities, caregiving for children or other persons, or caregiving for both children and others (multiple caregiving roles). Two multivariable marginal logistic regression models with repeated measures were fit (one each for patients and controls) to examine the effect of caregiving roles on elevated depressed mood, using generalized estimating equations to account for intra-individual correlations. Of 1096 participants (mean age 58; 76% white), 1019 with caregiving data were included in the analysis. Compared with baseline, patients with multiple caregiving roles (23/521 patients) were at increased risk of elevated depressed mood at 6 months (adjusted odds ratio [aOR], 7.20; 95% confidence interval [CI], 1.17-44.46; P = 0.034), and controls with multiple caregiving roles (15/498 controls) were at decreased risk of elevated depressed mood at 12-month follow-up (aOR, 0.12; 95% CI, 0.02-0.97; P = 0.047). Patients with multiple caregiving roles were more likely while controls were less likely to report elevated depressed mood over time, suggesting a need to identify patients with multiple caregiving roles early during their treatment.

A longitudinal study of factors associated with perceived risk of recurrence in women with ductal carcinoma in situ and early-stage invasive breast cancer.

Breast cancer patients' perceived risk of recurrence has been associated with psychological distress. Little is known about the change of patients' perceived risk of recurrence over time and factors associated with their recurrence-risk perceptions. We prospectively recruited 549 newly diagnosed early-stage breast cancer patients; patients completed interviews at 6 weeks, 6 months, 1 year, and 2 years after definitive surgical treatment. A random-effects regression model with repeated ordinal measurements was used to estimate the relationship between perceived risk of recurrence and demographic, medical, and psychosocial factors. We analyzed data from 535 patients [34% ductal carcinoma in situ (DCIS); 20% non-white] who reported their perceived risk at one or more interviews. At the first interview, 16% reported having no lifetime risk of recurrence, and another 16% reported ≥ 50% risk of recurrence, including 15% of DCIS patients. Patients who were white (OR = 5.88, 95% CI 3.39-10.19) and had greater state anxiety (OR = 1.04, 95% CI 1.02-1.07) were more likely, while patients who received radiotherapy (OR = 0.72, 95% CI 0.54-0.96) and had more social support (OR = 0.59, 95% CI 0.46-0.75) were less likely to report higher risk of recurrence. Cancer stage was not significantly associated with perceived risk of recurrence. Perceived risk of recurrence did not change significantly over time. Educating early-stage breast cancer patients about their actual risk could result in more realistic recurrence-risk perceptions, and increasing social support could help alleviate anxiety associated with exaggerated risk perceptions.

A gene expression signature that predicts the therapeutic response of the basal-like breast cancer to neoadjuvant chemotherapy.

Several gene expression profiles have been reported to predict breast cancer response to neoadjuvant chemotherapy. These studies often consider breast cancer as a homogeneous entity, although higher rates of pathologic complete response (pCR) are known to occur within the basal-like subclass. We postulated that profiles with higher predictive accuracy could be derived from a subset analysis of basal-like tumors in isolation. Using a previously described "intrinsic" signature to differentiate breast tumor subclasses, we identified 50 basal-like tumors from two independent clinical trials associated with gene expression profile data. 24 tumor data sets were derived from a 119-patient neoadjuvant trial at our institution and an additional 26 tumor data sets were identified from a published data set (Hess et al. J Clin Oncol 24:4236-4244, 2006). The combined 50 basal-like tumors were partitioned to form a 37 sample training set with 13 sequestered for validation. Clinical surveillance occurred for a mean of 26 months. We identified a 23-gene profile which predicted pCR in basal-like breast cancers with 92% predictive accuracy in the sequestered validation data set. Furthermore, distinct cluster of patients with high rates of cancer recurrence was observed based on cluster analysis with the 23-gene signature. Disease-free survival analysis of these three clusters revealed significantly reduced survival in the patients of this high recurrence cluster. We identified a 23-gene signature which predicts response of basal-like breast cancer to neoadjuvant chemotherapy as well as disease-free survival. This signature is independent of tissue collection method and chemotherapeutic regimen.

Micrometastatic disease and isolated tumor cells as a predictor for additional breast cancer axillary metastatic burden.

BACKGROUND: Our study aims were to investigate breast cancer patients with micrometastases or isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) to determine the rate of non-SLN metastasis and axillary recurrences, and to compare actual non-SLN metastasis rates with those predicted by the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. METHODS: We identified 116 stage I to III breast cancer patients who underwent sentinel lymph node biopsy and had micrometastases or ITCs (<2-mm deposits). Patients underwent completion axillary lymph node dissection (ALND) (group 1) or had no further axillary surgery (group 2). P < 0.05 was considered statistically significant. RESULTS: Of 116 patients with micrometastases or ITCs in SLNs, 55 (47%) underwent completion ALND (group 1), and 61 (53%) had no further axillary surgery (group 2). The rate of non-SLN metastases in group 1 patients was 9 (16%) of 55, which was significantly less than that predicted by the MSKCC nomogram (median 30%, P < 0.001). Patient age, race, tumor histology, tumor grade, estrogen receptor/Her-2neu status, and lymphovascular invasion did not differ significantly between group 1 patients with positive non-SLNs and those with negative non-SLNs (P > 0.05 for each), but patients with positive non-SLNs had larger tumors (P < 0.001). No patient in group 1 experienced an axillary recurrence, while only one patient (1.6%) in group 2 experienced axillary recurrence. CONCLUSIONS: The actual rate of positive non-SLNs for breast cancer patients with SLN micrometastases or ITCs who underwent completion ALND was significantly less than that predicted by the MSKCC nomogram. The rate of axillary recurrence is negligible, regardless of the extent of axillary staging.

Method of breast cancer presentation and depressed mood 1 year after diagnosis in women with locally advanced disease.

BACKGROUND: Differences in psychological outcomes of breast cancer patients with locally advanced disease who presented with abnormal screening mammograms or palpable mass have not been reported. METHODS: We interviewed 120 women with clinical stage II/III breast cancer enrolled onto a prospective phase 2 clinical trial at diagnosis and 1 year after diagnosis, inquiring about demographics, depressive symptoms, social support, and perceived risk of disease recurrence. Presentation method (abnormal screening mammogram or symptoms) was determined by chart review. Change in depressed mood was assessed by repeated measures analysis of covariance, grouping by presentation method. RESULTS: A significant interaction was observed between presentation method and change in depressed mood among 86 women without disease progression who completed both interviews. Women presenting with breast symptoms experienced a decrease and women presenting with abnormal screening mammogram experienced an increase in depressed mood (P = 0.032). CONCLUSIONS: Women diagnosed with locally advanced breast cancer by screening mammography showed increased depressed mood a year after diagnosis. Therefore, identification of locally advanced breast cancer by screening mammogram may be a risk factor for posttreatment depression.

Patient and tumor characteristics associated with increased mortality in young women (< or =40 years) with breast cancer.

BACKGROUND: The goal of the current study is to identify predictors responsible for mortality disparities between young (< or =40 years) and older (>40 years) women with breast cancer. METHODS: From 1998 to 2006, 344 patients < or =40 years were treated for breast cancer. Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) to determine differences in breast cancer mortality in women < or =40 years versus >40 years (n = 3,252), controlling for potential confounders in univariate tests. RESULTS: From 1998 to 2006, 3,596 patients were treated for breast cancer; 9.6% were < or =40 years and 90.4% were >40 years. Young women were more likely to be African-American, with a family history of breast cancer, diagnosed at advanced stage, and treated by mastectomy (P < 0.05). Tumors in young women were more likely to be bilateral, T2/T3, grade III, ER/PR negative, and lymph-node positive (P < 0.01). Overall, young women (< or =40 years) with breast cancer were more likely to die compared with older women (>40 years) (aHR 1.52, CI 1.37-1.74). CONCLUSIONS: Young women (< or =40 years) with breast cancer are diagnosed at a more advanced stage and have tumors with poor prognostic features. Young women (< or =40 years) are 52% more likely to die from breast cancer compared to older women (>40 years).

The impact of breast MRI on surgical decision-making: are patients at risk for mastectomy?

BACKGROUND AND OBJECTIVES: The goal of the current study was to determine whether MRI impacts multidisciplinary treatment planning and if it leads to increased mastectomy rates. METHODS: A retrospective review was conducted of 441 patients treated for breast cancer between January 2005 and May 2008 who underwent breast MRI. Data included number of additional findings and their imaging and pathologic work-up. This was analyzed to determine impact of MRI on treatment planning. RESULTS: Of 441 patients, 45% had > or =1 additional finding on MRI. Of 410 patients with complete records, 29% had changes in the treatment plan, including 36 patients who were initially considered for breast conservation but proceeded directly to mastectomy based on MRI findings of suspected multicentricity. Twenty-three of those patients did not have a biopsy of the MRI lesion, with 87% having unicentric disease on final pathology. Overall, the mastectomy rate was 44%, which was significantly increased compared to patients not undergoing MRI (32%, P < 0.05). CONCLUSIONS: Breast MRI alters the treatment planning for many patients with newly diagnosed breast cancer. Mastectomy rates are increased when MRI results alone direct surgical planning. Biopsy of MRI-identified lesions should be performed to avoid over-treatment.

Predictors of primary breast abscesses and recurrence.

BACKGROUND: We investigated the patients and microbiological risk factors that predispose to the development of primary breast abscesses and subsequent recurrence. METHODS: Patients with a primary breast abscess requiring surgical therapy between January 1, 2000 and December 31, 2006 were reviewed. Recurrent breast abscess was defined by the need for repeated drainage within 6 months. Patient characteristics were compared to the general population and between groups. RESULTS: A total of 89 patients with a primary breast abscess were identified; 12 (14%) were lactational and 77 (86%) were nonlactational. None of the lactational abscesses recurred, whereas 43 (57%) of the nonlactational abscesses did so (P < 0.01). Compared to the general population, patients with a primary breast abscess were predominantly African American (64% vs. 12%), had higher rates of obesity (body mass index > 30: 43% vs. 22%), and were tobacco smokers (45% vs, 23%) (P < 0.01 for all). The only factor significantly associated with recurrence in the multivariate logistic regression analysis was tobacco smoking (P = 0.003). Compared to patients who did not have a recurrence, patients with recurrent breast abscesses had a higher incidence of mixed bacteria (20.5% vs. 8.9%), anaerobes (4.5% vs. 0%), and Proteus (9.1% vs. 4.4%) but lower incidence of Staphylococcus (4.6% vs. 24.4%) (P < 0.05 for each). CONCLUSIONS: Risk factors for developing a primary breast abscess include African American race, obesity, and tobacco smoking. Patients with recurrent breast abscesses are more likely to be smokers and have mixed bacterial and anaerobic infections. Broader antibiotic coverage should be considered for the higher risk groups.

High-throughput, label-free, single-cell photoacoustic microscopy of intratumoral metabolic heterogeneity.

Intratumoral heterogeneity, which is manifested in almost all of the hallmarks of cancer, including the significantly altered metabolic profiles of cancer cells, represents a challenge to effective cancer therapy. High-throughput measurements of the metabolism of individual cancer cells would allow direct visualization and quantification of intratumoral metabolic heterogeneity, yet the throughputs of current measurement techniques are limited to about 120 cells per hour. Here, we show that single-cell photoacoustic microscopy can reach throughputs of approximately 12,000 cells per hour by trapping single cells with blood in an oxygen-diffusion-limited high-density microwell array and by using photoacoustic imaging to measure the haemoglobin oxygen change (that is, the oxygen consumption rate) in the microwells. We demonstrate the capability of this label-free technique by performing high-throughput single-cell oxygen-consumption-rate measurements of cultured cells and by imaging intratumoral metabolic heterogeneity in specimens from patients with breast cancer. High-throughput single-cell photoacoustic microscopy of oxygen consumption rates should enable the faster characterization of intratumoral metabolic heterogeneity.

Estrogen carcinogenesis: specific identification of estrogen-modified nucleobase in breast tissue from women.

Prolonged exposure to estrogens correlates with an increased risk for breast cancer. One explanation is that estrogen metabolites cause mutations by reacting with DNA, leading to depurination. We describe an extraction procedure and a liquid chromatographic tandem mass spectrometric (LC/MS/MS) assay to detect estrone-metabolite-modified adenine (Ade) in 100-200 mg samples of human breast tissue. To ensure reliable analyses, we used a synthetic estrone-metabolite-modified, U-(15)N-labeled Ade as an internal standard (IS). Appropriate high-pressure liquid chromatography gives sharp (approximately 5 s at half-height) and identical retention times for the analyte and the IS. In breast tissue from women with and without cancer, we found a coeluting material with similar MS/MS fragmentation as the IS, providing high specificity in the identification of the modified Ade; the recovery was approximately 50%. For women with and without breast cancer, the levels of the modified Ade are in the range of 20-70 fmol/g of breast tissue from five women and not detectable in tissue from another woman. The sample size and detection limits are not yet sufficient to permit distinctions between cancer and noncancer patients.