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Introduction: There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations., Methods: We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records., Results: Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival ( p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival ( p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors ( p = 0.008)., Conclusion: Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Sanaa Gamrani et al.)

Determination of human epidermal receptor protein-2 (HER2) is a crucial step in the treatment of patients diagnosed with invasive breast carcinoma. HER2 status is an independent clinical prognostic factor and a predictive factor of tumor response to chemotherapeutic agents such as trastuzumab. Accurate testing is necessary to offer adequate therapy to patients. To evaluate the variation in HER2 testing results, we analyzed our data from review cases in which HER2 testing was repeated at our institution from January 2013 to December 2014. For the study, the reason for repeating the test, the testing methodology used, and the tests results were collected. Concordance between outside and in-house HER2 results was compared. Discrepancies were classified as major and minor. A total of 173 cases were retested during this period. One-hundred and twenty-eight cases met the inclusion criteria. Sixteen cases were originally tested at large reference laboratories and two in international laboratories. In the 110 remaining cases, the test was performed at small community laboratories or the testing facility was not available. Forty-one (32%) discrepancies were identified. Of these, 15 (12% of 128 total) were major and 26 (20% of 128 total) were considered minor discrepancies. Our study confirms that significant discrepancies in HER2 results persist even after stricter and well-developed testing guidelines have been embraced., (© 2017 Wiley Periodicals, Inc.)

Molecular diagnostics in personalized medicine increasingly relies on the combination of a variety of analytical technologies to characterize individual diseases and to select patients for targeted therapies. The gold standard for tissue-based diagnostics is fixation in formalin and embedding in paraffin, which results in excellent preservation of morphology but negatively impacts on a variety of molecular assays. The formalin-free, non-cross-linking PAXgene tissue system preserves morphology in a similar way to formalin, but also preserves biomolecules essentially in a similar way to cryopreservation, which markedly widens the spectrum, sensitivity and accuracy of molecular analytics. In this study, we have developed and tested a protocol for PAXgene-fixed and paraffin-embedded tissues for fluorescent in situ hybridization (FISH). The implementation of a 24-h formalin postfixation step of slides from PAXgene-fixed and paraffin-embedded tissues allowed us to use the assays approved for formalin-fixed and paraffin-embedded tissues. The equivalence of the methodologies was demonstrated by FISH analysis of HER2 amplification in breast cancer cases. The 24-h postfixation step of the slides used for FISH can be well integrated in the routine diagnostic workflow and allows the remaining PAXgene-fixed and paraffin-embedded tissue to be used for further molecular testing., (© 2016 The Authors. International Journal of Experimental Pathology published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).)

Background: Women with benign breast disease (BBD) have an increased risk of developing breast cancer (BC). Nearly 30% of all BCs develop in women with prior BBD. Information regarding features of the expected number of BCs after BBD would enhance individualized surveillance and prevention strategies for these women. In the current study, the authors sought to characterize BCs developing in a large cohort of women with BBD., Methods: The current study cohort included 13,485 women who underwent breast biopsy for mammographic or palpable concerns between 1967 and 2001. Biopsy slides were reviewed and classified as nonproliferative disease, proliferative disease without atypia, or atypical hyperplasia. BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed., Results: With median follow-up of 15.8 years, 1273 women developed BC. The majority of BCs were invasive (81%), of which 61% were ductal, 13% were mixed ductal/lobular, and 14% were lobular. Approximately two-thirds of the BC cases were intermediate or high grade, and 29% were lymph node positive. Cancer characteristics were similar across the 3 histologic categories of BBD, with a similar frequency of ductal carcinoma in situ, invasive disease, tumor size, time to invasive BC, histologic type of BC, lymph node positivity, and human epidermal growth factor receptor 2 positivity. Women with atypical hyperplasia were found to have a higher frequency of estrogen receptor-positive BC (91%) compared with women with proliferative disease without atypia (80%) or nonproliferative disease (85%) (P = .02)., Conclusions: A substantial percentage of all BCs develop in women with prior BBD. The majority of BCs after BBD are invasive tumors of ductal type, with a substantial number demonstrating lymph node positivity. Of all the BCs in the current study, 84% were estrogen receptor positive. Prevention therapy should be strongly encouraged in higher-risk women with BBD., (© 2015 American Cancer Society.)

Background: The objective of the current study was to investigate the prognostic value of pretreatment [(18) F] fluorodeoxyglucose position emission tomography/computed tomography ([(18) F]FDG PET/CT) in patients with advanced-stage breast cancer., Methods: Pretreatment PET/CT scans from 240 consecutive patients with American Joint Committee on Cancer stage III or stage IV BC were analyzed retrospectively. Clinicopathological factors and metabolic parameters of the primary tumor including maximum standardized uptake value (SUVmax ), metabolic tumor volume, and total lesion glycolysis (TLG) with a range of thresholds were compared to predict progression-free survival (PFS) and overall survival (OS) using a time-dependent receiver operating characteristic curve and Cox proportional hazards regression analyses., Results: SUVmax with a cutoff value of 6.0, TLG30% with a cutoff value of 158 g, and phenotype associated with PFS and OS were analyzed using multivariate analysis. The mean TLG30% of primary tumors for patients with stage III and stage IV disease was 405 g and 750 g (P = .010), respectively. Patients with triple-negative breast cancer or a TLG30% >158 g or with both were categorized as being at high risk, and those with non-triple-negative breast cancer and a primary tumor with a TLG30% ≤158 g were defined as low risk. The 5-year PFS rates for stage III disease among patients with low-risk versus high-risk BC were 85% and 67.5%, respectively. For patients with stage IV disease, the 5-year PFS rates were 45% and 9%, respectively, for patients with low-risk versus high-risk disease. Patients with stage III and high-risk BC had OS rates that were similar to those for patients with stage IV and low-risk BC (P = .552)., Conclusions: The TLG30% from pretreatment PET/CT was found to independently correlate with survival outcomes and appears to be able to effectively stratify both patients with stage III and those with stage IV BC., (© 2015 American Cancer Society.)

Breast cancers that have negative or extremely low expression of estrogen receptor and progesterone receptor and non-amplification of human epidermal growth factor receptor-2 (HER2)/neu are termed triple-negative breast cancer (TNBC). The majority of TNBC tumors belong to the biologically aggressive basal subtype, and they cannot be managed with targeted endocrine or anti-HER2/neu agents. In western, high resource environments, risk factors for TNBC include younger age at diagnosis and hereditary susceptibility. Women of African ancestry in the United States and in continental Africa have higher frequencies of TNBC, prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer survival disparities related to racial/ethnic identity. Efforts to document and confirm the breast cancer burden of continental Africa have been hampered by the limited availability of registry and immunohistochemistry resources. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa, and to compare the frequencies as well as risk factors for TNBC versus non-TNBC in this large referral tertiary hospital. The Korle Bu Teaching Hospital is affiliated with the University of Ghana and is located in Accra, the capital of Ghana. We conducted an institutional, Department of Pathology-based review of the breast cancer cases seen at this facility for the 2010 calendar year, and for which histopathologic specimens were available. The overall study population of 223 breast cancer cases had a median age of 52.4 years, and most had palpable tumors larger than 5 cm in diameter. More than half were TNBC (130; 58.3%). We observed similar age-specific frequencies, distribution of stage at diagnosis and tumor grade among cases of TNBC compared to cases of non-TNBC. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively younger age at diagnosis compared to Caucasian Americans and African Americans. The triple-negative molecular marker pattern was the most common subtype of breast cancer seen among this sample of Ghanaian women, regardless of age, tumor grade, or stage of diagnosis. Research into the molecular pathogenesis of TNBC may help elucidate the reasons for its increased prevalence among women with African ancestry., (© 2015 Wiley Periodicals, Inc.)

The mean residual life function provides a clear and simple summary of the effect of a treatment or a risk factor in units of time, avoiding hazard ratios or probability scales, which require careful interpretation. Estimation of the mean residual life is complicated by the upper tail of the survival distribution not being observed as, for example, patients may still be alive at the end of the follow-up period. Various approaches have been developed to estimate the mean residual life in the presence of such right censoring. In this work, a novel semi-parametric method that combines existing non-parametric methods and an extreme value tail model is presented, where the limited sample information in the tail (prior to study termination) is used to estimate the upper tail behaviour. This approach will be demonstrated with simulated and real-life examples., (Copyright © 2015 John Wiley & Sons, Ltd.)

Trastuzumab-based chemotherapy has dramatically improved outcomes for patients with all stages of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Additional HER2-directed agents that have recently been approved are also expected to improve outcomes. Patients with small, lymph node-negative, HER2-positive breast cancers who are treated with trastuzumab-based chemotherapy demonstrate especially favorable responses, with 5-year recurrence rates of <5%. In this review, recent data regarding response rates among patients with early-stage HER2-positive breast cancer treated with trastuzumab-based chemotherapy are discussed. This review supports future studies of the possible omission of chemotherapy in a subset of patients with HER2-positive cancers, specifically those that coexpress hormone receptors., (© 2014 American Cancer Society.)

Background: The purpose of the current study was to describe the outcomes of patients with human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified (HER2+) early breast cancer who received adjuvant or neoadjuvant trastuzumab-based therapy and were subsequently retreated with trastuzumab for metastatic disease., Methods: A total of 353 patients with metastatic HER2+ breast cancer who were treated with trastuzumab as part of their first-line treatment for metastatic disease were identified. A total of 75 patients had received adjuvant or neoadjuvant trastuzumab-based therapy for early breast cancer, and 278 had not. Clinical outcomes of patients who had or had not received prior trastuzumab were compared using Cox proportional hazards regression and logistic regression analyses. Survival was estimated using the Kaplan-Meier method., Results: The clinical benefit (complete response, partial response, or stable disease of ≥ 6 months) rates were 71% in the group who did not receive prior trastuzumab and 39% in the group previously treated with trastuzumab. The adjusted odds ratios were 0.28 (95% confidence interval [95% CI], 0.13-0.59; P = .0009) for clinical benefit rates and 0.39 (95% CI, 0.18-0.82; P = .038) for objective (complete or partial) response rates. In the univariate analysis, the median overall survival rate was longer in the group who did not receive prior trastuzumab (36 months vs 28 months) (hazards ratio, 1.47; 95% CI, 1.07-2.01 [P = .022]). The multivariate analysis found no significant difference in overall survival., Conclusions: When treated with trastuzumab for metastatic disease, patients with HER2+ breast cancer without prior exposure to trastuzumab were found to have superior clinical outcomes to those with prior exposure. Prior trastuzumab exposure should be considered in treatment algorithms and in HER2-targeted clinical trial enrollment for metastatic disease., (© 2014 American Cancer Society.)

Background: The evidence regarding correlations between various anthropometric characteristics and breast cancer risk among young women is mixed, and few studies have assessed these associations by subtype., Methods: This was a population-based, case-control study of 779 women with estrogen receptor (ER)-positive breast cancer; 182 women with ER-negative/human epidermal growth factor-2 (HER2)-negative/progesterone receptor-negative (triple-negative [TN]) breast cancer; and 60 women with ER-negative/HER2-overexpressing, invasive breast cancer ages 20 to 44 years who were diagnosed from 2004 to 2010 in the Seattle-Puget Sound metropolitan area; as well as 939 cancer-free controls. Associations between height and body mass index (BMI) at different time points in relation to breast cancer risk were assessed using polytomous logistic regression., Results: Height, BMI at age 18 years, and BMI at the reference date were not related to the risks of ER-positive, TN, or HER2-overexpressing breast cancer. Changes in BMI from age 18 years to the reference date were not related to the risk of either ER-positive or HER2-overexpressing breast cancer. However, compared with women who had a BMI change from 0 to 4.9 kg/m(2) from age 18 years to the reference date, those who experienced a BMI increase ≥10 kg/m(2) during the same interval had a 2.0-fold (95% confidence interval, 1.2-fold to 3.3-fold increase) increased risk of TN breast cancer. For women with ER-positive disease, there was some evidence that parity modified the effect of BMI change (Pinteraction  = .002), because a BMI increase of ≥10 kg/m(2) was associated with a reduced risk of ER-positive disease only among nulliparous women (odds ratio, 0.3; 95% confidence interval, 0.2-0.6)., Conclusions: The correlations appear to differ substantially between BMI change and the risks of TN breast cancer and ER-positive breast cancer., (© 2014 American Cancer Society.)

Background: This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer., Methods: A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale)., Results: In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm., Conclusions: Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life., (© 2013 American Cancer Society.)

Background: Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in patients with esophageal adenocarcinoma (EAC), with gene amplification used as a selection criterion for treatment, although to the authors' knowledge the concordance between amplification and HER2 protein expression remains undefined in EAC. Furthermore, the association between HER2 and its interacting partner, human epidermal growth factor receptor 3 (HER3), is unknown yet appears to be of potential therapeutic relevance., Methods: Patients with untreated EACs (N = 673) were analyzed for HER2 amplification and polysomy 17 by fluorescence in situ hybridization in parallel with immunohistochemistry (IHC) (IHC scores of 0-1+, 2+, and 3+). Amplification was defined as HER2/CEP17 ≥ 2. HER3 expression by IHC was analyzed in randomly selected cases (n = 224). IHC and fluorescence in situ hybridization results were compared using least squares linear regression., Results: Overall, 17% of the EACs (116 of 673 EACs) were HER2-amplified with an amplification frequency that was highest among IHC3+ cases (89%) and declined among IHC2+ cases (13%) and IHC0 to IHC1+ cases (4%). Among HER2-amplified cases, the level of amplification increased linearly with HER2 membranous expression (HER2/CEP17 ratio: 7.9 in IHC3+ and 5.5 in IHC2+ vs 2.8 in IHC0 to IHC1+ [P < .0001]), with 14% of amplified tumors demonstrating absent/faint expression (IHC0 to IHC1+). Polysomy 17 was not found to be associated with HER2 expression. Cytoplasmic HER3 expression was detected in 87% of tumors (195 of 224 tumors) and was found to be significantly associated with better differentiation (P < .0001). Stepwise increases in HER3 expression were associated with higher HER2 expression levels (P = .0019)., Conclusions: Levels of HER2 protein expression and amplification were found to be linearly associated and highly concordant. Among amplified tumors with absent/faint expression, the level of amplification was low. Frequent expression of HER3 suggests its relevance as a therapeutic target, and its significant association with HER2 supports ongoing efforts to inhibit HER2/HER3 in patients with EAC., (© 2013 American Cancer Society.)

Background: Data suggest that weight, and specifically body mass index (BMI), plays a role in breast cancer development and outcome. The authors hypothesized that there would be a correlation between BMI and clinical outcome in patients with early stage, human epidermal receptor 2 (HER2)-positive breast cancer enrolled in the N9831 adjuvant trial., Methods: Patients were grouped according to baseline BMI as follows: normal (BMI <25 kg/m(2)), overweight (BMI ≥25 kg/m(2) and <30 kg/m(2)), and obese (BMI ≥30 kg/m(2)). Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Comparisons between treatment arms A, B, and C (chemotherapy with or without trastuzumab) were performed using a stratified Cox proportional hazards model., Results: Analysis was completed on 3017 eligible patients. Obese patients were more likely to be older and postmenopausal (P < .0001 for both), to have larger tumors (P = .002), and to have positive lymph nodes (P = .004). In the pooled analysis cohort, differences in DFS among the BMI groups were statistically significant (5-year DFS rate: 82.5%, 78.6%, and 78.5% for normal weight, overweight, and obese women, respectively; log-rank P = .02). The adjusted hazard ratio comparing the DFS of overweight women with the DFS of normal women was 1.30 (95% confidence interval, 1.06-1.61); and, comparing the DFS of obese women with the DFS normal women, the adjusted hazard ratio was 1.31 (95% confidence interval, 1.07-1.59). There were no statistically significant differences in DFS by weight group for women within any trial arm., Conclusions: Patients with early stage, HER2-positive breast cancer and normal BMI had a better 5-year DFS compared with overweight and obese women. The current results indicated that adjuvant trastuzumab improves clinical outcome regardless of BMI., (Copyright © 2013 American Cancer Society.)

Background: The objective of this study was to evaluate and identify patterns of failure and prognostic factors for locoregional recurrence (LRR) that could justify postmastectomy radiotherapy after modified radical mastectomy in patients with early stage triple-negative breast cancer., Methods: Between January 2000 and July 2007, the authors retrospectively analyzed 390 patients who had triple-negative breast cancer with T1/T2 tumors and from zero to 3 positive lymph nodes (pathologic T1-T2N0-N1) who underwent modified radical mastectomy without postmastectomy radiotherapy at the author's institution. The 5-year cumulative incidence for events was calculated using Kaplan-Meier analysis, and subgroups were compared using the log-rank test. Multivariate analysis was performed using a Cox proportional hazards model., Results: Overall, 86.4% of patients received chemotherapy. At a median follow-up of 60.5 months, the 5-year cumulative rates of local recurrence, regional recurrence, LRR, and distant metastasis were 5.4%, 4.7%, 8%, and 13.4%, respectively. On multivariate analysis, age <50 years, the presence of lymphovascular invasion, grade 3 tumor, and 3 involved lymph nodes were associated significantly with an increased risk of LRR. The 5-year LRR rate for patients who had 0 or 1 risk factor, 2 risk factors, and 3 or 4 risk factors was 4.2%, 25.2%, and 81% (P < .0001), respectively. The presence of lymphovascular invasion and having 3 involved lymph nodes were statistically significant predictors of regional recurrence, and the patients who had regional recurrence had a significantly greater risk of distant metastases compared with patients who had local recurrence (59.1% vs 20.9%; P < .0001)., Conclusions: Several risk factors were identified in this study that correlated independently with a greater incidence of LRR in patients who had early stage triple-negative breast cancer. The current results indicated that postmastectomy radiotherapy should be considered for those patients who have 2 or more of these factors., (Copyright © 2013 American Cancer Society.)

Background: Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer have prompted interest in whether patients who achieved a pCR can be identified preoperatively and potentially spared the morbidity of surgery. The objective of this multicenter, retrospective study was to estimate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting a pCR in the breast., Methods: MRI studies at baseline and after the completion of NCT plus data regarding pathologic response were collected retrospectively from 746 women who received treatment at 8 institutions between 2002 and 2011. Tumors were characterized by immunohistochemical phenotype into 4 categories based on receptor expression: hormone (estrogen and progesterone) receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 327), HR-positive/HER2-positive, (n = 148), HR-negative/HER2-positive, (n = 101), and triple-negative (HR-negative/HER2 negative; n = 155). In all, 194 of 249 patients (78%) with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed., Result: For the total group, the rCR and pCR rates were 182 of 746 patients (24%) and 179 of 746 patients (24%), respectively, and the highest pCR rate was observed for the triple-negative subtype (57 of 155 patients; 37%) and the HER2-positive subtype (38 of 101 patients; 38%). The overall accuracy of MRI for predicting pCR was 74%. The variables sensitivity, negative predictive value, positive predictive value, and accuracy differed significantly among tumor subtypes, and the greatest negative predictive value was observed in the triple-negative (60%) and HER2-positive (62%) subtypes., Conclusions: The overall accuracy of MRI for predicting pCR in invasive breast cancer patients who were receiving NCT was 74%. The performance of MRI differed between subtypes, possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves the predictive value of MRI for pathologic response., (Copyright © 2013 American Cancer Society.)

Background: We conducted a phase 1, multicenter, open-label, dose-escalation study (TDM3569g) to assess the safety, tolerability, and pharmacokinetics of single-agent trastuzumab emtansine (T-DM1) administered weekly and once every 3 weeks in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab. The weekly dose results are described here., Methods: Patients were administered escalating doses of T-DM1 weekly, starting at 1.2 mg/kg. Additional patients were enrolled at the maximum tolerated dose (MTD) to better characterize tolerability and pharmacokinetics., Results: Twenty-eight patients received weekly T-DM1, and the MTD was determined to be 2.4 mg/kg. In general, T-DM1 was well tolerated, requiring few dose modifications or discontinuations because of adverse events (AEs). Grade ≥ 3 AEs were reported in 19 patients (67.9%); treatment-related AEs occurred in 25 (89.3%) patients. Exposure to weekly T-DM1 was dose-proportional at ≥ 1.2 mg/kg, and accumulation of T-DM1 and total trastuzumab was observed. Objective partial tumor responses were reported in 13 (46.4%) patients; the median duration of response was 18.6 months, and the 6-month clinical benefit rate was 57.1%., Conclusion: The results suggest that a weekly dose of T-DM1 2.4 mg/kg has antitumor activity and is well tolerated in patients with HER2-positive metastatic breast cancer., (Copyright © 2012 American Cancer Society.)

Background: Obesity has been associated with inferior outcomes in operable breast cancer, but the relation between body mass index (BMI) and outcomes by breast cancer subtype has not been previously evaluated., Methods: The authors evaluated the relation between BMI and outcomes in 3 adjuvant trials coordinated by the Eastern Cooperative Oncology Group that included chemotherapy regimens with doxorubicin and cyclophosphamide, including E1199, E5188, and E3189. Results are expressed as hazard ratios (HRs) from Cox proportional hazards models (HR >1 indicates a worse outcome). All P values are 2-sided., Results: When evaluated as a continuous variable in trial E1199, increasing BMI within the obese (BMI, ≥ 30 kg/m(2)) and overweight (BMI, 25-29.9 kg/m(2)) ranges was associated with inferior outcomes in hormone receptor-positive, human epidermal growth receptor 2 (HER-2)/neu-negative disease for disease-free survival (DFS; P = .0006) and overall survival (OS; P = .0007), but not in HER-2/neu-overexpressing or triple-negative disease. When evaluated as a categorical variable, obesity was associated with inferior DFS (HR, 1.24; 95% confidence interval [CI], 1.06-1.46; P = .0008) and OS (HR, 1.37; 95% CI, 1.13-1.67; P = .002) in hormone receptor-positive disease, but not other subtypes. In a model including obesity, disease subtype, and their interaction, the interaction term was significant for OS (P = .02) and showed a strong trend for DFS (P = .07). Similar results were found in 2 other trials (E5188, E3189)., Conclusions: In a clinical trial population that excluded patients with significant comorbidities, obesity was associated with inferior outcomes specifically in patients with hormone receptor-positive operable breast cancer treated with standard chemohormonal therapy., (Copyright © 2012 American Cancer Society.)

The association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status of breast cancer patients with total choline (tCho) concentration and tumor volume was investigated using in vivo proton magnetic resonance spectroscopy and MRI at 1.5 T. Values for tCho concentration were determined in 120 locally advanced breast cancer patients (stages IIB, IIIA, IIIB, and IIIC), 31 early breast cancer patients (stage IIA), 38 patients with benign lesions, and 37 controls. Significantly higher tCho concentration and lower tumor volume were observed in early breast cancer patients compared to locally advanced breast cancer patients (P<0.05). tCho concentration and tumor volume did not correlate with age and menstruation. tCho cutoff values were obtained for the differentiation of malignant from benign breast tissues (2.54 mmol/kg); malignant versus normal (1.45 mmol/kg) and benign versus normal tissues (0.82 mmol/kg). Estrogen receptor negative patients showed significantly larger tumor volumes, indicating higher angiogenesis with aggressive tumor behavior. Nontriple negative and triple positive patients had a significantly higher tCho concentration compared to triple negative patients (P<0.05), indicating complex molecular mechanism of cell proliferation and the molecular heterogeneity of breast lesions. The results indicate the potential use of integration of breast 1H magnetic resonance spectroscopy in diagnostic workup., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: This retrospective study sought to define the incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer (TNBC)., Methods: A total of 2448 patients with stage I through III TNBC who were diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. The Kaplan-Meier product limit method was used to compute survival following a diagnosis of brain metastases., Results: At a median follow-up of 39 months, 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95% confidence interval [CI] = 2.9%-4.5%) and 5.4% (95% CI = 4.4%-6.5%), respectively. Among patients with stage I, II, and III disease, the 2-year cumulative incidence of brain metastases was 0.8%, 3.1%, and 8%, respectively (P < .0001). The 5-year cumulative incidence was 2.8%, 4.6%, and 9.6% among patients with stage I, II, and III disease, respectively (P < .0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (hazards ratio = 3.51; 95% CI = 1.85-6.67; P = .0001) compared to patients with stage I disease. Those with stage II disease had a nonsignificant increased risk of developing brain metastases as a first site of recurrence (hazards ratio = 1.61; 95% CI = 0.92-2.81; P = .10) compared with patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range, 5.7-9.4 months)., Conclusions: Patients with nonmetastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort in which to research preventive strategies., (Copyright © 2012 American Cancer Society.)

Background: The authors conducted exploratory phase 1-2 clinical trials vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) A2/A3-restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent disease recurrence. They previously reported that the vaccine is safe and effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they report 24-month landmark analyses of disease-free survival (DFS)., Methods: These dose escalation/schedule optimization trials enrolled lymph node-positive and high-risk lymph node-negative patients with HER2 (immunohistochemistry [IHC] 1-3(+) ) expressing tumors. HLA-A2/A3(+) patients were vaccinated; others were followed prospectively as controls for recurrence. DFS was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests., Results: Of 195 enrolled patients, 182 were evaluable: 106 (58.2%) in the vaccinated group and 76 (41.8%) in the control group. The 24-month landmark analysis DFS was 94.3% in the vaccinated group and 86.8% in the control group (P = .08). Importantly, because of trial design, 65% of patients received a lower than optimal vaccine dose. In subset analyses, patients who benefited most from vaccination (vaccinated group vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08). A booster program has been initiated; no patients receiving booster inoculations have recurred., Conclusions: The E75 vaccine has clinical efficacy that is more prominent in certain patients. A phase 3 trial enrolling lymph node-positive patients with HER2 low-expressing tumors is warranted., (Copyright © 2011 American Cancer Society.)

Background: Growth factor receptors such as epidermal growth factor receptor 1 and human epidermal growth receptor 2 (HER2) are overexpressed in certain cancer cells. Antibodies against these receptors (eg. cetuximab and transtuzumab [Herceptin]) have shown therapeutic value in cancer treatment. The existing methods for the quantification of these receptors in tumors involve immunohistochemistry or DNA quantification, both in extracted tissue samples. The goal of the study was to evaluate whether an optical fiber-based technique can be used to quantify the expression of multiple growth factor receptors simultaneously., Methods: The authors examined HER2 expression using the monoclonal antibody trastuzumab as a targeting ligand to test their system. They conjugated trastuzumab to 2 different Alexa Fluor dyes with different excitation and emission wavelengths. Two of the dye conjugates were subsequently injected intravenously into mice bearing HER2-expressing subcutaneous tumors. An optical fiber was then inserted into the tumor through a 30-gauge needle, and using a single laser beam as the excitation source, the fluorescence emitted by the 2 conjugates was identified and quantified by 2-photon optical fiber fluorescence., Results: The 2 conjugates bound to the HER2-expressing tumor competitively in a receptor-specific fashion, but they failed to bind to a similar cell tumor that did not express HER2. The concentration of the conjugate present in the tumor as determined by 2-photon optical fiber fluorescence was shown to serve as an index of the HER2 expression levels., Conclusions: These studies offer a minimally invasive technique for the quantification of tumor receptors simultaneously., (Copyright © 2011 American Cancer Society.)

Purpose: To evaluate the impact of low estrogen/progesterone receptor (ER/PR) expression and effect of endocrine therapy on survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative tumors with ER/PR <10%, previously labeled as triple negative., Methods: In a retrospective review, 1257 patients were categorized according their ER/PR percentages into 3 groups, ER/PR <1% (group A), ER/PR 1% to 5% (group B), and ER/PR 6% to 10% (group C). Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics., Results: Groups A, B, and C had 897 (71.4%), 241 (19.2%), and 119 (9.4%) patients, respectively. After a median follow-up of 40 months there was no significant difference in 3-year recurrence-free survival (RFS): 64%, 67%, and 77% (P = .34) or overall survival (OS): 79%, 81%, and 88% (P = .33) for groups A, B, and C, respectively. ER/PR expression was not an independent predictor for RFS (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.86-1.39; P = .46 for group B, and HR, 0.96; 95% CI, 0.66-1.38; P = .81 for group C, compared with group A), or OS (HR, 1.11; 95% CI, 0.84-1.46; P = .46 for group B, and HR, 0.94; 95% CI, 0.63-1.42; P = .78 for group C, compared with group A). Endocrine therapy had no impact on survival outcomes (RFS: P = .10; OS: P = .45) among groups., Conclusions: In this cohort, a low ER/PR level (1%-5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6% to 10% is seen. Benefit of endocrine therapy in these patients is unclear., (Copyright © 2011 American Cancer Society.)

Background: Increased use of breast cancer screening has led to an increase in the number of diagnosed cases of ductal carcinoma in situ (DCIS). However, there is no definite way to predict progression or recurrence of DCIS. We analyzed the significance of biological markers and tumor characteristics in predicting recurrence in a large series of DCIS patients with long-term follow-up treated with breast conservation surgery (BCS) alone., Methods: Clinical and pathological data were analyzed for 141 patients who underwent BCS for DCIS. All had negative surgical margins. Using local disease recurrence as an endpoint, we sought to determine the prognostic significance of several histopathological characteristics (tumor size, presence of necrosis, and subtype) and biological markers (estrogen receptor, progesterone receptor, and Her-2/neu.), Results: At a median follow-up of 122 months (maximum follow-up, 294 months), 60 recurrences occurred, with a median time to recurrence of 191 months. On multivariate analysis, Her-2 positivity (3+) was found to be significantly associated with reduced time to tumor recurrence (P = .028). Tumor size and higher grade were marginally statistically significant (P = .099, P = .070). Neither necrosis nor tumor pathological characteristics were found to be significantly related to time to disease recurrence., Conclusions: Our results suggested that status of Her-2/neu, larger tumor size, and higher nuclear grade were significantly correlated with time to tumor recurrence in patients treated with BCS alone. Using logistical analyses, no significant correlation was found between tumor pathological characteristics and disease recurrence., (Copyright © 2011 American Cancer Society.)

To evaluate overall survival (OS), disease-free survival (DFS), and local-recurrence free survival (LRFS) rates in a subgroup of patients affected by breast cancer expressing a particular phenotype (estrogen receptor negative, progesterone receptor negative, and Human Epidermal Growth Factor receptor 2 negative) known as "triple negative" (TN). Data of 387 women affected by early breast cancer who underwent whole-breast radiotherapy after conservative surgery with or without chemotherapy and/or hormone therapy between January 2002 and December 2008, in the Department of Radiotherapy at Regional Cancer Center, were retrospectively evaluated. Chi-squared test was used to compare prognostic factors (age, histology, tumor size, nodal status, grading, and adjuvant therapy) between TN patients and non-TN patients. OS, DFS, and LRFS rates were analyzed using Kaplan--Meier proportional log-rank test; impact of prognostic factors on poor outcome was evaluated using Cox regression stepwise method on univariate and multivariate analysis. Mean follow-up time was 57.6 months (range13.7-109.7). TN patients were more likely to have ≥T2 tumors (p = 0.0003), grade 3 tumors (p = 0.0001) and to receive chemotherapy as adjuvant therapy (p =< 0.0001). TN patients had lower 5-years-OS (p = 0.039) and lower 5-years-DFS (p = 0.003) compared with non-TN patients. No difference in 5-years LRFS was found (p = 0.49). After multivariate analysis, TN status was found to be a predictive factor for OS (p = 0.004) and for DFS (p = 0.01), but not for LRFS (p = 0.8). TN patients have lower survival when compared with non-TN patients, but similar LRFS rates. These patients can be treated in a conservative surgical protocol, but should receive more aggressive and tailored adjuvant therapies., (© 2011 Wiley Periodicals, Inc.)

Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER-2) have a predilection to metastasize to the brain. Therapeutic options for brain metastases with systemic therapy remain a challenge in those patients since targeted and chemotherapeutic agents have limited penetration through the blood-brain barrier. Here we report the case of a patient with brain metastases from breast cancer overexpressing HER-2 who achieved a complete radiologic response after treatment by radiation and concurrent Lapatinib and Capecitabine., (© 2010 Wiley Periodicals, Inc.)

The purpose of this study is to report further about the statistically significant results from a prospective study, which suggests that fusion of prone F-18 Fluoro-deoxy-glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) breast scans increases the positive predictive value (PPV) and specificity for patients in whom the MR outcome alone would be nonspecific. Thirty-six women (mean age, 43 years; range, 24-65 years) with 90 lesions detected on MR consented to undergo a FDG-PET scan. Two blinded readers evaluated the MR and the computer tomography (CT) attenuation-corrected prone FDG-PET scans side-by-side, then after the volumes were superimposed (fused). A semiautomatic, landmark-based program was used to perform nonrigid fusion. Pathology and radiologic follow-up were used as the reference standard. The sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy (with 95% confidence intervals) for MR alone, FDG-PET alone, and fused MR and FDG-PET were calculated. The median lesion size measured from the MR was 2.5 cm (range, 0.5-10 cm). Histologically, 56 lesions were malignant, and 15 were benign. Nineteen lesions were benign after 20-47 months of clinical and radiologic surveillance. The sensitivity of MR alone was 95%, FDG-PET alone was 57%, and fusion was 83%. The increase in PPV from 77% in MR alone to 98% when fused and the increase in specificity from 53% to 97% were statistically significant (p < 0.05). The false-negative rate on FDG-PET alone was 26.7%, and after fusion this number was reduced to 9%. FDG-PET and MR fusions were helpful in selecting which lesion to biopsy, especially in women with multiple suspicious MR breast lesions.

This study reports the value of the tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in predicting the response of breast cancer to neoadjuvant chemotherapy. A community cancer center prospectively maintained breast cancer database containing over 8,000 patient records was used. Since 1989, 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR. Estrogen receptor and/or PR positive patients were considered hormone receptor (HR) positive. Human epidermal growth factor receptor 2 status was available on 368 patients. Total, breast, and nodal pathologic complete response (pCR) rates, recurrence, and overall survival were assessed. Total and breast pCR rates were higher in HR negative (HR-) patients (26% and 32%, respectively) than in HR positive (HR+) patients (4% and 7%, respectively; p < 0.001). Compared to HR+ patients, HR- patients had higher recurrence rates (38% versus 22%; p < 0.001), a shorter time to recurrence (1.28 versus 2.14 years; p < 0.001), and decreased overall survival (67% versus 81%; p < 0.001). Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab (NAT) demonstrated higher total pCR (34% versus 13%; p = 0.008), breast pCR (37% versus 17%; p = 0.02), and nodal pCR rates (47% versus 23%; p = 0.05) compared to HER2+ patients not treated with NAT. Furthermore, HER2+ patients who received NAT had lower recurrence rates (5% versus 42%; p < 0.001) and increased overall survival (97% versus 68%; p < 0.001). In conclusion, breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy. Although HR- patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response, they have worse outcomes in terms of recurrence and survival. Hormone receptor positive patients demonstrate significantly less response to neoadjuvant chemotherapy, but significantly better overall outcome. For both HR- and HR+, addition of NAT for HER2+ tumors results in both a superior response and outcome.

Background: Although US year 2000 guidelines recommended characterizing breast cancers by human epidermal growth factor receptor 2 (HER2), national cancer registries do not collect HER2, rendering a population-based understanding of HER2 and clinical "triple subtypes" (estrogen receptor [ER] / progesterone receptor [PR] / HER2) largely unknown. We document the population-based prevalence of HER2 testing / status, triple subtypes and present the first report of subtype incidence rates., Methods: Medical records were searched for HER2 on 1842 metropolitan Atlanta females diagnosed with breast cancer during 2003-2004. HER2 testing/status and triple subtypes were analyzed by age, race/ethnicity, tumor factors, socioeconomic status, and treatment. Age-adjusted incidence rates were calculated., Results: Over 90% of cases received HER2 testing: 12.6% were positive, 71.7% negative, and 15.7% unknown. HER2 testing compliance was significantly better for women who were younger, of Caucasian or African-American descent, or diagnosed with early stage disease. Incidence rates (per 100,000) were 21.1 for HER2+ tumors and 27.8 for triple-negative tumors, the latter differing by race (36.3 and 19.4 for black and white women, respectively)., Conclusions: HER2 recommendations are not uniformly adhered to. Incidence rates for breast cancer triple subtypes differ by age/race. As biologic knowledge is translated into the clinical setting eg, HER2 as a biomarker, it will be incumbent upon national cancer registries to report this information. Incidence rates cautiously extrapolate to an annual burden of 3000 and 17,000 HER2+ tumors for black and white women, respectively, and triple-negative tumors among 5000 and 16,000 respectively. Testing, rate, and burden variations warrant population-based in-depth exploration and clinical translation., ((c) 2010 American Cancer Society.)

Background: Testing technologies are increasingly used to target cancer therapies. Human epidermal growth factor receptor 2 (HER2) testing to target trastuzumab for patients with breast cancer provides insights into the evidence needed for emerging testing technologies., Methods: The authors reviewed literature on HER2 test utilization and cost effectiveness of HER2 testing for patients with breast cancer. They examined available evidence on: percentage of eligible patients tested for HER2; test methods used; concordance of test results between community and central/reference laboratories; use of trastuzumab by HER2 test result; and cost effectiveness of testing strategies., Results: Little evidence was available to determine whether all eligible patients are tested, how many are retested to confirm results, and how many with negative HER2 test results still receive trastuzumab. Studies suggested that up to 66% of eligible patients had no documentation of testing in claims records, up to 20% of patients receiving trastuzumab were not tested or had no documentation of a positive test, and 20% of HER2 results may be incorrect. Few cost-effectiveness analyses of trastuzumab explicitly considered the economic implications of various testing strategies., Conclusions: There was little information about the actual use of HER2 testing in clinical practice, but evidence suggested important variations in testing practices and key gaps in knowledge exist. Given the increasing use of targeted therapies, it is critical to build an evidence base that supports informed decision making on emerging testing technologies in cancer care.

Intracystic papillary carcinoma (IPC), a breast tumor mainly occuring in the elderly, has long been considered as a variant of ductal carcinoma in situ (DCIS). This is now debated since metastatic cases have been reported. In this study, surgical pieces of 20 IPCs were reassessed, and markers of myopepithelial layer (p63, CD10 and Smooth Muscle Actin) as well as estrogen receptors (ER) and progesterone receptors (PgR) and C-erb-B2 oncoprotein expression were systematically performed and quantified. In 10 cases, an associated unequivocal invasive component was found. In all 20 cases, no myoepithelial layer was found. Eighteen tumors were ER positive, 14 were PgR positive. Moreover, none of the tumors over-expressed C-erb-B2 oncoprotein. Therefore this study showed that in all cases of IPC there were microscopic features of invasive carcinoma despite good clinical prognostic indicators, and that precise characterization of tumors requires extensive paraffin embedding of surgical pieces.

Breast cancer research examining either molecular profiles or biomarker subtypes has focused on the estrogen receptor negative/progesterone receptor negative/human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) and ER-/PR-/HER2+ subtypes. Less is known about the epidemiology or clinical outcome of the other subtypes. This study examines the eight combinations of ER/PR/HER2 in patients with invasive breast cancer. The 5-year relative survival and the distribution among demographic, socioeconomic, and tumor characteristics of each of the subtypes are examined. Using the California Cancer Registry, 61,309 women with primary invasive breast cancer were classified according to ER/PR/HER2 status. Five-year relative survival was computed for the eight subtypes. Bivariate analyses were used to assess the distribution of cases across all subtypes. Multivariate logistic regression was used to compute the adjusted odds of having one of the five subtypes with the best and worst survival. Survival varied from 96% (ER+/PR+/HER2-) to 76% (ER-/PR-/HER2+ and ER-/PR-/HER2-). The four subtypes with the poorest survival were all ER negative. Women who were younger than age 50, non-Hispanic black or Hispanic, of the lowest SES groups, and had stage IV tumors that were undifferentiated were overrepresented in ER-/PR-/HER2+ and triple negative (ER-/PR-/HER2-) subtypes. Asian Pacific Islanders had increased odds (OR = 1.41; 95% confidence interval [CI] = 1.26-1.57) of having the ER-/PR-/HER2+ subtype. Stage III tumors (OR = 1.25; 95% CI = 1.08-1.44) and stage IV tumors (OR = 1.58; 95% CI = 1.27-1.98) had higher odds than stage I tumors of being ER-/PR-/HER2+. Stage IV tumors (OR = 0.54; 95% CI = 0.44-0.67) strongly decreased the odds of the ER-/PR-/HER2- subtype. Poorly differentiated and undifferentiated tumors were over 20 times as likely as well-differentiated tumors of being ER-/PR-/HER2- or ER-/PR-/HER2+. There are considerable differences in survival, demographics, and tumor characteristics among the eight subtypes. We recommend reporting breast cancer as an ER/PR/HER2 subtype and precisely documenting demographic and tumor characteristics.

Objective: To investigate the prognostic value of HER2 and p63 expression in head and neck squamous cell carcinoma (HNSCC)., Study Design: A case review of 186 HNSCCs from the oral tongue, palate, maxillary sinus, floor of mouth, oropharynx, hypopharynx, and larynx., Subjects and Methods: All primary tumor specimens were evaluated by immunohistochemistry for HER2 and p63 expressions, which were correlated with clinical parameters including age, sex, grade, lymph node metastases, stage, and survival., Results: One hundred forty-one patients had stage III-IV disease and 109 had lymph node metastases. For all cases, T and N stages were significant prognostic predictors for both overall and disease-free survivals. In the node-positive subgroup, T stage and HER2 expression were significant prognostic predictors for both overall and disease-free survivals., Conclusion: HER2 may be associated with longer survival in node-positive patients with HNSCC.

Pregnancy-associated breast cancer (PABC) is a rare and challenging problem. We sought to describe epidemiology, management and outcome of women in whom breast cancer was diagnosed during pregnancy or within one year after delivery. Thirty-two women with PABC were referred to two European Union oncology centers between 1995 and 2007, 16 during pregnancy and 16 within 1 year after delivery. Data concerning diagnosis, management, delivery and fetal and maternal outcome were recorded. A group of 32 patients (matched controls) presenting with nonpregnancy-associated breast cancer (non-PABC) was matched for age at diagnosis, tumor size and stage to each PABC patient. Differences in outcome between the PABC and non-PABC groups were then assessed. Histological features were similar in both groups, except that estrogen receptor-negative tumors were more common in the PABC group. Three patients received chemotherapy and two others underwent surgery during pregnancy, with no excess toxicity or severe maternal/fetal adverse effects. All children in the PABC group were healthy, except for one exposed to epirubicin in utero and born with rectal atresia. Overall survival was similar in PABC and non-PABC patients (p = 0.449). The subgroup of patients with breast cancer diagnosed within one year after delivery showed a shorter time to relapse than controls or patients with gestational cancer (p = 0.0178). PABC is a special situation, necessitating individualized, multi-disciplinary management. Prognosis is similar for women with nongestational cancer matched for age and stage though poorer outcome postpartum should be further investigated.

Background: Fine-needle aspiration (FNA) is a rapid and accurate procedure for the detection of breast carcinomas. The evaluation of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression by immunohistochemistry (IHC) is performed routinely on formalin-fixed, paraffin-embedded needle-core (NC) or excision tissue block (TB) preparations, according to the American Society of Clinical Oncology/College of American Pathologist guidelines. In this retrospective study, the authors compared expression levels of ER, PR, and HER2 in ethanol-fixed BC FNA cell block (CB) samples with expression levels in formalin-fixed NC and TB samples., Methods: Forty-one breast carcinoma CB samples with concurrent or subsequent NC and TB samples were identified. Patients who had received neoadjuvant or adjuvant chemotherapy were excluded. CB samples initially were fixed in 50% ethanol (4-12 hours), and this was followed by formalin fixation (minimum, 6 hours). NC samples were placed promptly in formalin for a minimum of 6 hours. Within 4 to 8 hours, TB samples were fixed in formalin for 6 to 48 hours. Fluorescence in situ hybridization (FISH) results were also compared., Results: IHC for ER on alcohol-fixed CB samples had good correlation with NC and TB samples. PR results on TB samples had excellent agreement with NC samples. A higher discordance rate wais observed when PR results were compared between CB samples and NC samples. HER2 detection on ethanol-fixed CB samples resulted in a higher rate of positive and equivocal staining than NC or TB samples. HER2 IHC on TB samples demonstrated better correlation with FISH results than CB or NC samples., Conclusions: Alcohol fixation did not affect ER results in breast carcinoma, but it may alter tumor cell PR antigenicity. The authors concluded that CB samples could be used to triage patients for tamoxifen therapy, but they are not reliable for the assessment of HER2 status; therefore, CB results should be correlated with results from NC or TB samples., (Copyright 2009 American Cancer Society)

Background: Because distinguishing between multiple primary lung cancers and intrapulmonary metastasis is often difficult when the tumor histology is same, the feasibility of analyzing differential protein expression profiles to distinguish multiple primary lung cancers from intrapulmonary metastasis was evaluated., Methods: This study enrolled 50 patients, with multiple primary lung cancers demonstrating the same histology, who underwent surgery between April 1994 and March 2006 and 20 patients who were diagnosed to have intrapulmonary metastasis during the same period. Thirty patients with lymph-node metastasis were selected for comparison purposes. The sum value of the differences in the expression ratio of 4 proteins (p53, p16, p27, and c-erbB2) was evaluated in immunohistochemically stained specimens among multiple primary lung cancers and intrapulmonary metastasis., Results: None of the 30 patients with lymph-node metastasis showed a sum value of the differences between primary tumor and lymph-node metastasis in the 4 protein expression ratios>90. Therefore, when the difference between 2 tumors exceeded 90, the 2 tumors were considered to be different from each other, ie, multiple primary lung cancers. Forty-one of 50 (82%) patients who were clinically diagnosed to have multiple primary lung cancers showed a sum value of the differences in their protein expression ratios>90, 4 of 20 (20%) patients who were clinically diagnosed to have intrapulmonary metastasis showed a sum value>90. Among the patients who were clinically diagnosed to have multiple primary lung cancers and intrapulmonary metastasis, the 5-year survival of 70 patients who had a sum value of the differences in their 4 protein expression ratios, either >90 (newly classified multiple primary lung cancers) and