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Introduction: To evaluate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of ZRC-3277 (pertuzumab biosimilar) with Perjeta® (pertuzumab) in previously untreated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC)., Patients and Methods: This phase III, multicenter, double-blind study across 38 sites in India randomized (1:1) patients with HER2-positive MBC in either the ZRC-3277 or Perjeta® group. Both groups also received trastuzumab and docetaxel. Of 268 enrolled patients, mITT population had 243 patients (119 and 124 in the ZRC-3277 and Perjeta® groups, respectively). The primary objective was to compare the between-group objective response rate (ORR) after 6 cycles of treatment. ORR was determined by evaluating scans of computed tomography or magnetic resonance imaging following Response Evaluation Criteria in Solid Tumor (RECIST 1.1). Two-sided 95% confidence interval (95% CI) for the difference in ORR was determined to evaluate the noninferiority of ZRC-3277 to Perjeta®. The secondary outcomes included the assessment of PK, immunogenicity, and safety between the 2 groups., Results: In the mITT population, 104 (87.39%) and 114 (91.94%) participants achieved the ORR in the ZRC-3277 and Perjeta® groups, respectively. For predefined -15% noninferiority margin, obtained 2-sided 95% CIs (-12.19%, 3.11%) for the difference in ORR (-4.55%) between the 2 groups demonstrated the noninferiority of ZRC-3277 to Perjeta®. PK, immunogenicity, and safety were not significantly different between the 2 groups., Conclusion: Efficacy, PK, immunogenicity, and safety profiles of ZRC-3277 was found to be similar to those of Perjeta®., Competing Interests: Disclosure Deven Parmar is an employee of Zydus Therapeutics Inc, USA, whereas Maulik Doshi and Rahul Shrivastava are employees of Zydus Lifesciences Ltd. All other authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Breast cancer is an intricate disease that is increasing at a fast pace, and numerous heterogeneities within it further make it difficult to investigate. We have always used animal models to understand cancer pathology and create an in vivo microenvironment that closely resembles human cancer. They are considered an indispensable part of any clinical investigation regarding cancer. Animal models have a high potency in identifying the relevant biomarkers and genetic pathways involved in the course of disease prognosis. Researchers have previously explored a variety of organisms, including Drosophila melanogaster, zebrafish, and guinea pigs, to analyse breast cancer, but murine models have proven the most comprehensive due to their homologous nature with human chromosomes, easy availability, simple gene editing, and high adaptability. The available models have their pros and cons, and it depends on the researcher to select the one most relevant to their research question. Chemically induced models are cost-effective and simple to create. Transplantation models such as allografts and xenografts can mimic the human breast cancer environment reliably. Genetically engineered mouse models (GEMMs) help to underpin the genetic alterations involved and test novel immunotherapies. Virus-mediated models and gene knockout models have also provided new findings regarding breast cancer progression and metastasis. These mouse models have also enabled the visualization of breast cancer metastases. It is also imperative to consider the cost-effectiveness of these models. Despite loopholes, mouse models have evolved and are required for disease analysis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Targeted second-look ultrasound (US) is often performed following MRI of the breast to determine if an MRI-detected lesion is visible on US and thus amenable to US-guided biopsy. This study aimed to assess the pathology of lesions detected and biopsied on the second-look US. In particular, for multifocal cancers, whether the pathology of additional lesions detected by second-look US is different to the index lesion., Methods: Multicentre single-institution retrospective study of 300 consecutive cases of second-look US biopsies from August 2017 to April 2022 was performed, with their histopathology and imaging characteristics recorded. For multifocal cancers, Wilcoxon Signed Ranks Tests were used to compare differences between the index and additional lesions in the histopathology category (i.e., high-risk benign, precursor or malignant) and BRE grade., Results: 69 multifocal cancers were detected. For the purposes of this study, additional lesions were considered more invasive if they were of a higher histopathological category or BRE grade, or demonstrated lymphovascular invasion when the primary lesion did not. 15/69 additional lesions were not seen on the initial mammogram/tomography or ultrasound, seen on subsequent MRI and second look US, and were less invasive than the index lesion. 3/69 additional lesions were more invasive than their index lesions. Wilcoxon Signed Ranks test showed additional lesions were of either similar or lesser invasiveness compared to index lesions (z= -3.207, p  = 0.001) in the histopathological category, and the same or lower BRE grade (z= -2.972, p  = 0.003)., Conclusion: In multifocal breast cancers, additional lesions detected on MRI and second-look US have the same or less invasive histopathology compared to the index lesion.

Polymeric magnetic nanoparticles have shown higher efficacy in cancer diagnosis and treatment than conventional chemotherapies. Lignin is an abundantly available natural polymer that can be selectively modified using a rapidly expanding toolkit of biocatalytic and chemical reactions to yield 'intelligent' theranostic-nanoprobes. We aim to valorize lignin to develop a natural polymeric-magnetic-nano-system for the targeted delivery of methotrexate. In the current study, we synthesized nanoparticles of lignin and iron oxide with methotrexate using a new approach of anti-solvent precipitation with ultrasonication. The ensuing nanoparticles are magnetic, smooth, polyhedral with characteristic dimension of 110-130 nm. The drug loading and encapsulation efficiencies were calculated to be 66.06 % and 64.88 %, respectively. The nanoparticles exhibit a concentration-dependent release of methotrexate for the initial 24 h, followed by sustained release. Moreover, formulation is non-hemolytic and scavenges radicals owing to the antioxidant property of lignin. Additionally, methotrexate delivered using the nanoparticles exhibited higher cytotoxicity in cellular-viability assays employing breast cancer and macrophage cell lines compared to the pure form of the drug. Synergistic action of lignin, iron oxide, and methotrexate contribute to enhanced caspase-3 activity and reduced glutathione levels in the breast cancer cells, as well as elevated internalization of the drug on account of increased receptor-mediated endocytosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Yoga improved fatigue and immunological profile in cancer survivors and has been a promising alternative therapy. Breast cancer treatments are rapidly improving, along with their side effects. This article investigated the effect of the yogic intervention at a different time interval during radiotherapy/chemotherapy on the pro- and anti-inflammatory interleukins along with the cancer-related fatigue and functional scale among patients with stage II/III breast cancer., Methods: A total of 96 stage II/III breast cancer patients were enrolled in this study and randomly divided into two different groups. Group I (non-Yoga) received chemotherapy and/or radiotherapy and group II (Yoga) received an additional yogic intervention. Both groups were followed up for a period of 48 weeks and blood was collected at the time of enrollment, 16, 32, and 48 weeks, and serum was isolated to measure the pro- and anti-inflammatory interleukins, fatigue, and functional scale questionnaire obtained at each time point., Results: Breast cancer patients in group II showed a significant improvement (p < 0.05) in the functional scale and fatigue from baseline to 48 weeks compared to group I. The yogic intervention significantly decreased (p < 0.05) the level of pro-inflammatory interleukin IL-1β and pleiotropic interleukin IL-10 in group II compared to group I., Conclusion: These finding suggested that improved fatigue and functional scale is associated with a lower level of IL-1β and IL-10. Yoga may be an important additional therapy along with the cancer treatment to help the patients with cancer-related fatigue and improve their overall immunological profile., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Resistance to HER2 (ErbB2)-targeted therapy may be mediated by other members of the ErbB family. We investigated the efficacy and safety of the irreversible ErbB family blocker, afatinib, alone as first-line therapy in the advanced setting and in combination with vinorelbine or paclitaxel for those who progressed on afatinib monotherapy, in female patients with metastatic breast cancer who had failed or progressed on prior HER2-targeted therapy in the early disease setting., Methods: In this phase II, single-arm, two-part study (ClinicalTrials.gov: NCT01271725), patients in part A received afatinib 40 mg/day in 21-day cycles until disease progression or intolerable adverse events (AEs). Patients with progressive disease could then receive afatinib plus weekly vinorelbine 25 mg/m 2 or paclitaxel 80 mg/m 2 until disease progression or intolerable AEs (part B). The primary endpoint was confirmed objective response rate (RECIST v1.1)., Results: Eighty-seven patients were enrolled and 74 were treated in part A (median age: 51 years [range 27-76]; 31 [42%] estrogen receptor-positive, 26 [35%] progesterone receptor-positive). Of these, 39 (53%) patients went on to receive afatinib plus vinorelbine (13 patients) or paclitaxel (26 patients) in part B. Thirteen (18%) and 12 (31%) patients achieved an objective response in parts A and B, respectively. The most common treatment-related AEs with afatinib monotherapy (any/grade ≥ 3) were diarrhea (68%/8%) and rash (49%/4%). Combination therapy was generally well tolerated, with no additive toxicity observed., Conclusion: Afatinib treatment, alone or in combination with vinorelbine or paclitaxel, was associated with objective responses in ≥ 18% of patients with metastatic breast cancer for whom prior HER2-targeted therapy has failed. Treatment-related AEs were generally manageable, with few grade ≥ 3 AEs reported., Trial Registration: ClinicalTrials.gov, NCT01271725, registered 1 July 2011., (© 2022. The Author(s).)

Breast Cancer (BC) has the highest incidence among all forms of malignancies detected in women globally. The therapeutic approaches available for BC include chemotherapy, radiation therapy, hormonal therapy, and surgery. Recently, advanced immunology-based therapeutics with potential for BC treatment, including immune checkpoint blockades, vaccines, and combinations with other treatment strategies, have emerged. Although commonly used treatments such as trastuzumab/ pertuzumab for human epidermal growth factor receptor 2-positive BC and hormone therapy for estrogen receptor-positive and/or progesterone receptor-positive BC are specific, triple-negative BC cases remain a great challenge for treatment measures. Immune checkpoint inhibitors (anti- PD-1/anti-CTLA-4) and anti-cancer vaccines (NeuVax, MUC-1, AVX901, INO-1400, and CEA), either alone or in combination with other therapies, represent a new paradigm in cancer therapeutics. In this review, we highlight the current immunotherapeutic aspects and ongoing trials aimed at the development of better treatment regimens for BC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies often have detrimental side-effects, along with acquired resistance, with increased cancer recurrence. Thus, there is an urgent need to identify novel AIs with fewer side effects and improved therapeutic efficacies. In this regard, we and others have recently suggested noncoding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), as potential molecular targets for utilization in modulating cancer hallmarks and overcoming drug resistance in several cancers, including ER-positive breast and ovarian cancer. Herein, we describe the disruptive functions of several miRNAs and lncRNAs seen in dysregulated cancer metabolism, with a focus on the gene encoding for aromatase (CYP19A1 gene) and estrogen synthesis as a novel therapeutic approach for treating ER-positive breast and ovarian cancers. Furthermore, we discuss the oncogenic and tumor-suppressive roles of several miRNAs (oncogenic miRNAs: MIR125b, MIR155, MIR221/222, MIR128, MIR2052HG, and MIR224; tumor-suppressive miRNAs: Lethal-7f, MIR27B, MIR378, and MIR98) and an oncogenic lncRNA (MIR2052HG) in aromatase-dependent cancers via transcriptional regulation of the CYP19A1 gene. Additionally, we discuss the potential effects of dysregulated miRNAs and lncRNAs on the regulation of critical oncogenic molecules, such as signal transducer, and activator of transcription 3, β-catenin, and integrins. The overall goal of this review is to stimulate further research in this area and to facilitate the development of ncRNA-based approaches for more efficacious treatments of ER-positive breast and ovarian cancer patients, with a slight emphasis on associated treatment-delivery mechanisms.

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification.

Background: Limited data are available on the epidemiology of breast cancer (BC) in India., Objective: To study the epidemiological characteristics of BC patients attending a tertiary care hospital in National Capital Territory of India., Materials and Methods: A cross-sectional study was conducted and information from 320 women with confirmed BC was collected on a questionnaire for demographic profile, socioeconomic status (SES), reproductive risk factors, and family history of BC. Information on clinical presentation and staging of BC was recorded. Anthropometric assessment for body mass index (BMI) was done. Data were analyzed and presented as mean ± standard deviation and frequency tables., Results: The mean age at diagnosis of BC was 47 ± 10 years. Fifty-three percent of patients were illiterate or only primary school education. About 74% of patients were from urban areas. Only 11% of patients were from upper SES and 26% from lower SES. Forty-seven percent of patients had stage II followed by 36% with stage III BC. About 15% patients had experienced early menarche (<13 years of age) and 15% of women had attained late menopause (>51 years of age). About 42% of patients had <3 children and 15% patients had a family history of BC. About 38% patients were overweight and 21% were obese., Conclusion: Other than the established risk factors, other factors such as lack of education, SES, and higher BMI were present in our study. A higher percentage of women were diagnosed with BC at later stages. There is a need for educating women about BC, self-examination of breast, and screening programs for early detection of BC., Competing Interests: None

To study the nutritional risk factors and status of serum 25(OH)D levels in patients with breast cancer. A total of 100 women (cases) with confirmed breast cancer (BC) matched with equal number of healthy females (controls) of similar age and socioeconomic status (SES) were included in study. Controls included were nonbreast cancer patients who accompanied the patients to a tertiary care hospital. All the subjects (cases and controls) were administered a questionnaires to collect data on socioeconomic status, dietary pattern and the frequency of food consumption using a validated food frequency questionnaire. Anthropometric assessment was done for waist and hip circumference to calculate waist to hip ratio (WHR). Non fasting blood samples were collected for serum 25-hydroxyvitamin D [25(OH)D] levels estimation using chemiluminescent immunoassay technique and total serum calcium levels by colorimetric assay technique. Serum 25(OH)D and total calcium levels were expressed in ng/ml and mg/dl. Vitamin D deficiency was defined as per the guidelines set by United States Endocrine Society. The mean age of cases and controls was 45±9 and 46±10 years respectively. On multivariate analysis, an inverse association with BC was found for less frequency of fruits consumption with an adjusted (ORs, 95% CI) (2.7, 0.5-15.7) respectively. Mushroom intake was inversely associated with risk of BC (ORs, 95% CI) (5.6, 1.9-16.6). Saturated fat intake and high WHR were significantly associated with high risk of BC with adjusted ORs, 95% CI of (3.4, 1.4-8.1) and (5, 1.4-17). A significant association (p<0.05) was found between low serum 25(OH)D levels and the risk of BC with adjusted ORs, 95% CI of (2.5, 0.9-7.4). Majority of the patients with BC were suffering from vitamin D deficiency. Dietary intake of mushrooms containing vitamin D naturally was found to be associated with decreased risk of breast cancer. A significant association was found between low serum 25(OH)D levels (<20ng/ml) with the risk of BC. Obesity as a consequence of nutritional risk factors determined by higher WHR was found to be significantly associated with the risk of BC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The study was conducted with an objective to investigate the association between reproductive factors, nutritional status and serum 25(OH)D levels among women diagnosed with breast cancer (BC). A total of 200 women with BC attending a tertiary healthcare institute of Delhi, India matched with 200 healthy women for age (±2years) and socio economic status were included in the study. Data was collected on socio-demographic profile, reproductive factors, physical activity and dietary intake (24h dietary recall and food frequency questionnaire) using interviewer administered structured questionnaires and standard tools. Non fasting blood samples (5ml) were collected for the biochemical estimation of serum 25(OH)D and calcium levels by chemiluminescent immunoassay and colorimetric assay technique. Data was analyzed by univariable conditional logistic regression and significant variables with (p<0.05), were analyzed in final model by conditional multivariable logistic regression analysis. The mean age of patients at diagnosis of BC was 45±10years. Results of multivariable conditional logistic regression analysis revealed significantly higher odds of BC for reproductive factors like age at marriage (more than 23 years), number of abortions, history or current use of oral contraceptive pills (OCP), with [OR (95% CI)] of [2.4 (1.2-4.9)], [4.0 (1.6-12.6)], [2.4 (1.2-5.0)]. Women with physically light activities and occasional consumption of eggs were found to have higher odds of BC [4.6 (1.6-13.0)] and [3.2 (1.6-6.3)]. Women with serum 25(OH)D levels less than 20ng/ml and calcium levels less than 10.5mg/dl had higher odds of having BC [2.4 (1.2-5.1)] and [3.7 (1.5-8.8)]. A protective effect of urban areas as place of residence and energy intake greater than 50% of Recommended Dietary Allowance (RDA) per day against BC was observed (p<0.05). The findings of the present study revealed a significant association of reproductive and dietary factors in addition to sedentary physical activity and low serum 25(OH)D levels in women diagnosed with BC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Screening for breast cancer in high-risk women takes about 40 minutes to acquire an MRI scan and is time-intensive to report. There is recent interest in the performance of an abbreviated MRI protocol (FAST) in the screening setting. FAST scans have a reported negative predictive value of 99.8%. This study evaluates the false positive rates (FPR) and recall rates for FAST scans as compared to full diagnostic studies (FD)., Methods: A database of all screening breast MRI scans performed at our institution between 30 June 2013 and 1 July 2014 (n = 591) was created by one of the researchers, who did not subsequently analyse the MRI scans. The T1W and first post-contrast and subtracted images from each of these scans (FAST protocol) were assessed by experienced breast MRI radiologists, blinded to the final diagnosis. The findings were then compared with the FD result., Results: The recall rates were 6.6% for FAST scans and 5.8% for FD scans. FPR rates were 4.7% and 3.9% respectively. There is no statistically significant difference in the recall rates or FPR of FAST scans in comparison with full diagnostic studies., Conclusions: Given the absence of statistically significant difference in the FPR and recall rates in comparison with FD, FAST scans can replace FD for screening of breast cancer., (© 2016 The Royal Australian and New Zealand College of Radiologists.)

Background & Objectives: The proto-oncogene HER2/neu has been extensively studied in breast cancer patients. Serum levels of HER2/neu by ELISA in breast cancer patients were compared with tissue HER2/neu expression and with other clinicopathological parameters with the aim to investigate whether the serum assay could replace the established tests (IHC/FISH) for HER-2 status., Methods: Blood and Tru-cut biopsy samples were collected for determining HER2/neu status in 64 breast cancer patients. The tissue specimens were processed routinely and immunohistochemistry (IHC) for HER2/ER/PR (oestrogen/progesterone receptors) performed. Fluorescence in-situ hybridization (FISH) was performed on all HER2/neu 2 positive cases. Sixty age matched healthy females and females with benign breast disease were taken as controls for ELISA., Results: Of the 64 breast cancer cases, 25 (39.1%) had elevated serum HER2/neu levels accompanied with increased tissue expression of HER2/neu receptors. On IHC, HER2/neu score was 3+ in 24 (37.5%) cases, 2+ in three (4.6%), 1+ in 18 (28.1%); while 19 cases (29.7%) showed no HER2/neu expression. o0 f the three 2+ cases on IHC, two showed amplification on FISH. Twenty one (32.8%) patients were ER positive and 17 (26.6%) were PR positive. There was a significant correlation (P<0.001) of serum HER2 concentration with tumour size, lymph node involvement, stage of disease and histological grade. Serum HER2/neu levels showed a negative correlation with ER status (P=0.047) but no correlation with PR status., Interpretation & Conclusions: The results suggest that elevated serum HER2 level was associated with a clinicopathological aggressive phenotype of breast carcinoma and was related to tissue HER2 overexpression. Therefore, serum HER2 may be useful for monitoring the course of the disease and response to treatment., Competing Interests: None.

Background: Fibroepithelial lesions of the breast are classified into fibroadenoma and phyllodes tumor (PT). Although WHO has established a well-defined grading system for PT, dilemma of discriminating borderline from malignant PT still exists. Stromal CD10 is a known poor prognostic factor in invasive breast cancer, its expression in fibroepithelial lesions of the breast is not well-documented. Till date, only one study has correlated the CD10 staining score with tumor grade in PT., Objective: To evaluate whether the differences in expression patterns of CD10 and staining intensity correlate with the degree of malignancy in fibroepithelial tumors of the breast., Materials and Methods: This is a retrospective study in which stromal CD10 expression was studied in 75 cases of fibroepithelial lesions of the breast using immunohistochemistry. Statistical analysis was performed using Chi-square test., Results: There was a statistically significant trend of increasing stromal expression of CD10 with increasing degree of malignancy (P = 0.001)., Conclusions: CD10 staining pattern and its scoring can assist the pathologist to accurately grade the PT of the breast for adequate treatment and can also be used as a target for the development of novel therapies.

Aim: To study the clinical and epidemiological profile of patients of breast cancer presenting at our center at New Delhi, India and to evaluate the applicability of Gail model 2 as a means of measuring 5-year and lifetime risk in our already diagnosed cases of breast cancer., Methods: This was a retrospective study conducted at Lady Hardinge Medical College Hospital in New Delhi, India, between January 2011 and July 2014. Two hundred and twenty two diagnosed cases of breast cancer were included. Information was collected retrospectively on a Performa from the medical record section and the Pathology department of the hospital.The predicted five-year and lifetime risk was calculated using GM2 prediction model from the NCI's breast cancer risk assessment tool website., Results and Conclusions: Breast cancer in India is a far more biologically aggressive disease than in the west with a widely different spectrum of presentation and behavior and late presentation in an advanced stage. The accepted risk factors routinely associated with breast cancer in western literature do not appear to be relevant in the Indian population. Accepted western models do not seem to apply in the Indian scenario.

The transcription factor Kruppel-like factor 2 (KLF2) displays anticarcinogenic activities but the mechanism that underlies this activity is unknown. We show here that KLF2 is markedly downregulated in human breast cancers and that its expression positively correlates with breast cancer patient survival. We show further that KLF2 suppresses tumor development by controlling the transcriptional activity of the vitamin A metabolite retinoic acid (RA). RA regulates gene transcription by activating two types of nuclear receptors: RA receptors (RARs), which inhibit tumor development, and peroxisome proliferator-activated receptor β/δ (PPARβ/δ), which promotes tumorigenesis. The partitioning of RA between these receptors is regulated by two carrier proteins: cellular retinoic acid-binding protein 2 (CRABP2), which delivers RA to RARs, and fatty acid-binding protein 5 (FABP5), which shuttles ligands to PPARβ/δ. We show that KLF2 induces the expression of CRABP2 and RARγ and inhibits the expression FABP5 and PPARβ/δ thereby shifting RA signaling from the pro-carcinogenic FABP5/PPARβ/δ to the growth-suppressing CRABP2/RAR path. The data thus reveal that KLF2 suppresses tumor growth by controlling the transcriptional activities of RA.

Objectives: This retrospective study was designed to present the clinical characteristics and histopathological features of Primary neuroendocrine carcinoma (PNEC) of breast, and to evaluate the impact on outcome following its management on the line of more common primary adenocarcinoma of breast., Materials and Methods: Records of four patients diagnosed with PNEC of breast were retrospectively reviewed. Data were obtained from medical record from January 2008 to December 2012. Diagnosis of PNEC was confirmed by histopathological examination (HPE) and immunohistochemical (IHC) staining of tissue obtained from Trucut biopsy of the breast lump in all four patients. PNEC of breast was defined by the presence of more than 50% of invasive tumor cells with cytoplasmic immunoreaction for neuroendocrine (NE) markers synaptophysin, chromogranin or neuron specific enolase as per WHO classification. All patients were treated with Modified Radical Mastectomy (MRM), six cycle of Cyclophosphamide, Adriamycin and 5-Flurouracil (CAF) based adjuvant chemotherapy, radiotherapy and hormonal therapy., Results: There were four female patients. The mean age was 58~years (50-65 years). Breast lump was the presenting complaint in all patients. The result of HPE showed tumor size ranging from 4 to 6.5 cm in diameter. Axillary lymph node metastasis was detected in three (75%) patients. ER and PR expression was positive in four (100%) and three patients (75%) respectively. None of the patients expressed Her-2-neu. IHC staining was positive for NE markers chromogranin in three (75%) patients, synoptophysin in two patients (50%) and Neuron specific enolase three (75%) patients. The mean follow-up time was 27.7 months (range 48-9). All four patients survived without any loco-regional or metastatic recurrence with one patient developing lymphedema of arm., Conclusions: Breast lump is the most common presentation of PNEC of the breast with characteristic expression of NE markers by the tumor. Management of this rare tumor may include surgery, chemotherapy, radiotherapy and hormonal therapy depending on the size of the tumor, lymph node and hormone receptor status. However, most appropriate treatment plan has yet to be established.

Introduction: Current studies indicate that triple negative breast cancer (TNBC), an aggressive breast cancer subtype, is associated with poor prognosis and an early pattern of metastasis. Emerging evidence suggests that MUC4 mucin is associated with metastasis of various cancers, including breast cancer. However, the functional role of MUC4 remains unclear in breast cancers, especially in TNBCs., Method: In the present study, we investigated the functional and mechanistic roles of MUC4 in potentiating pathogenic signals including EGFR family proteins to promote TNBC aggressiveness using in vitro and in vivo studies. Further, we studied the expression of MUC4 in invasive TNBC tissue and normal breast tissue by immunostaining., Results: MUC4 promotes proliferation, anchorage-dependent and-independent growth of TNBC cells, augments TNBC cell migratory and invasive potential in vitro, and enhances tumorigenicity and metastasis in vivo. In addition, our studies demonstrated that MUC4 up-regulates the EGFR family of proteins, and augments downstream Erk1/2, PKC-γ, and FAK mediated oncogenic signaling. Moreover, our studies also showed that knockdown of MUC4 in TNBC cells induced molecular changes suggestive of mesenchymal to epithelial transition. We also demonstrated in this study, for the first time, that knockdown of MUC4 was associated with reduced expression of EGFR and ErbB3 (EGFR family proteins) in TNBC cells, suggesting that MUC4 uses an alternative to ErbB2 mechanism to promote aggressiveness. We further demonstrate that MUC4 is differentially over-expressed in invasive TNBC tissues compared to normal breast tissue., Conclusions: MUC4 mucin expression is associated with TNBC pathobiology, and its knockdown reduced aggressiveness in vitro, and tumorigenesis and metastasis in vivo. Overall, our findings suggest that MUC4 mucin promotes invasive activities of TNBC cells by altering the expression of EGFR, ErbB2, and ErbB3 molecules and their downstream signaling.

Background: We conducted a phase 2b, randomised, double-blind, placebo-controlled screening trial to evaluate the addition of the multikinase inhibitor sorafenib (antiproliferative/antiangiogenic) to first-line paclitaxel for human epidermal growth factor receptor 2 (HER2)-negative locally recurrent/metastatic breast cancer., Methods: Patients were randomised to paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off) plus sorafenib (400mg, orally, twice daily) or placebo. The primary endpoint was progression-free survival (PFS). A sample size of 220 patients was planned with relative risk ≤ 0.82 (1-sided α=0.14) after 120 events supporting a treatment effect., Findings: Patients were randomised in India (n=170), the United States (n=52) and Brazil (n=15). Median PFS was 6.9 months for sorafenib versus 5.6 months for placebo (hazard ratio (HR)=0.788; 95% confidence interval (CI), 0.558-1.112; P=0.1715 [1-sided P=0.0857]). The addition of sorafenib increased time to progression (median, 8.1 versus 5.6 months; HR=0.674; 95% CI 0.465-0.975; P=0.0343) and improved overall response (67% versus 54%; P=0.0468). Overall survival did not statistically differ (median, 16.8 versus 17.4 months; HR=1.022; 95% CI 0.715-1.461; P=0.904). Grade 3/4 toxicities (sorafenib versus placebo) included hand-foot skin reaction (31% versus 3%), neutropenia (13% versus 7%) and anaemia (11% versus 6%). Two treatment-related deaths occurred (malaria and liver dysfunction) in the sorafenib arm., Interpretation: The addition of sorafenib to paclitaxel improved disease control but did not significantly improve PFS to support a phase 3 trial of similar design. Toxicity of the combination was manageable with dose reductions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: CD10 is a zinc-dependent peptidase (metalloproteinase). Stromal CD10 expression in breast cancer correlates with poor prognosis, oestrogen receptor negativity and higher grade. CD10 may be a potential target of new cancer therapies as it is involved in cleavage of doxorubicin., Aim: To evaluate the effect of neo-adjuvant anthracycline-based chemotherapy on status of stromal CD10 antigens in breast cancer., Materials and Methods: Patients with invasive breast cancer scheduled for anthracycline-based neo-adjuvant chemotherapy were included in the study. Tumor stromal CD10 expression was estimated before and after 3 cycles of chemotherapy, and change in its status was correlated with clinical response to chemotherapy., Results: 16 out of the 29 patients had strong CD10 expression; in these 16 patients, 14 (87.5%) were hormone receptor negative, and 14 (87.5%) had HER-2/neu overexpression. Stromal CD10 expression remained same in 13 out of 29 cases (44.83%) after chemotherapy. There was a change in CD10 expression in the remaining 16 cases (55.17%); in 13 cases (44.83%) it decreased from its pre-chemotherapy status, while its expression increased in 3 cases (10.34%). In cases of complete and partial clinical response, there was no increase in CD10 expression. Where CD10 expression had increased after chemotherapy, there was either a minor response or no response to chemotherapy. In 13 cases where CD10 expression had decreased, 12 cases had a clinical response to chemotherapy., Conclusions: Strong CD10 expression correlates with hormone receptor negativity and HER-2/neu overexpression. Stromal CD10 expression in breast cancer is not static and changes with neo-adjuvant anthracycline-based chemotherapy. A stable or decrease in CD10 expression correlates with complete or partial clinical response, while an increase in CD10 expression appears to correlate with poor clinical response. A larger series is required to determine the clinical significance of these changes. As stromal CD10 expression and its change with chemotherapy may have a prognostic significance, they should be documented in breast cancer patients before and after chemotherapy.

Primary breast carcinoma is a common pathology in the UK. It can present with metastatic deposits but it is rare that lesions in the breast are the sole primary or secondary presentation for metastatic cancer from other sources. We present a case of a primary peritoneal cancer recurring after optimal treatment with a new breast lesion and the diagnostic difficulties that this can cause.

Mucins are high molecular weight, multifunctional glycoproteins comprised of two structural classes-the large transmembrane mucins and the gel-forming or secreted mucins. The primary function of mucins is to protect and lubricate the luminal surfaces of epithelium-lined ducts in the human body. Recent studies have identified a differential expression of both membrane bound (MUC1, MUC4 and MUC16) and secreted mucins (MUC2, MUC5AC, MUC5B and MUC6) in breast cancer tissues when compared with the non-neoplastic breast tissues. Functional studies have also uncovered many unique roles of mucins during the progression of breast cancer, which include modulation in proliferative, invasive and metastatic potential of tumor cells. Mucins function through many unique domains that can form complex association with various signaling molecules including growth factor receptors and intercellular adhesion molecules. While there is growing information about mucins in various malignancies including breast cancer, no focused review is there on the expression and functional roles of mucins in breast cancer. In this present review, we have discussed the differential expression and functional roles of mucins in breast cancer. The potential of mucins as diagnostic and prognostic markers and as therapeutic targets in breast cancer have also been discussed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We report a case of a patient with carcinoma breast who was incidentally diagnosed to be also suffering from Paget's disease of bone on a routine radionuclide bone scan. CT-guided biopsy and histopathology later confirmed the diagnosis.

Recent studies suggest that elevated body iron levels may contribute to breast carcinogenesis; however, epidemiologic evidence is lacking. We used data from a large cohort study of Canadian women to assess breast cancer in association with total iron and heme iron intake. Among 49,654 women ages 40 to 59 followed for an average of 16.4 years, we identified 2,545 incident breast cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate total dietary iron and heme iron intake. Using Cox proportional hazards models, we found no association of iron or heme iron intake with risk of breast cancer overall, in women consuming 30+ g of alcohol per day, or in women who had ever used hormone replacement therapy. The present study offers no support for an association of iron or heme iron intake with breast cancer risk or for a modification by iron of the effect of alcohol or estrogen. However, further cohort studies with repeated measurement of iron intake are warranted.

While there is evidence that breast cancer risk is positively associated with body mass index (in postmenopausal women) and energy intake and inversely associated with physical activity, few studies have examined breast cancer risk in association with energy balance, the balance between energy intake and expenditure. Therefore, in the cohort study reported here, we studied the independent and combined associations of vigorous physical activity, energy consumption, and body mass index (BMI), with breast cancer risk. The investigation was conducted in 49,613 Canadian women who were participants in the National Breast Screening Study (NBSS) and who completed self-administered lifestyle and food frequency questionnaires between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. During a mean 16.4 years of follow-up, we observed 2545 incident breast cancer cases. Due to exclusions for various reasons, the analyses were based on 40,318 subjects amongst whom there were 1673 incident cases of breast cancer. Participation in vigorous physical activity and body mass index were not independently associated with breast cancer risk in the total cohort. A statistically significant positive trend was observed, however, between energy intake and breast cancer risk (P (trend )= 0.01). Although there was some variation in risk associated with vigorous physical activity, and BMI when the analyses were stratified by menopausal status, these interactions were not statistically significant. The interaction between menopausal status and energy intake, however, was of borderline statistical significance (P (interaction )= 0.06), with a statistically significant increased risk of breast cancer associated with highest versus lowest quartile of energy intake among premenopausal women (Hazard Ratio [HR] = 1.45, 95% confidence interval [CI] = 1.13- 1.85, P (trend) = 0.001). There was evidence of an increased risk of breast cancer associated with a relatively high body mass index among postmenopausal women in the highest quartile level of energy intake (Hazard Ratio [HR] = 1.72, 95% confidence interval [CI] = 1.01- 2.93, P (trend) = 0.05). In addition, there was evidence of an increased risk of breast cancer among premenopausal, physically inactive, overweight/obese women who consumed > or =1972 kcal/day compared to physically active normal weight women who consumed <1972 kcal/day (HR = 1.60, 95% CI = 1.08-2.37). Our data suggest that obese premenopausal women with relatively high energy intake may be at increased risk of breast cancer. In addition, energy imbalance, represented by a relatively high energy intake, lack of participation in vigorous physical activity, and a relatively high body mass index, may be associated with increased breast cancer risk, particularly among premenopausal women.

Aim: To determine the incidence of pre-malignant and malignant conditions in radial scars identified from screening mammograms in women taking part in the UK NHS breast cancer screening programme., Methods: All women in our screening population from 1988 to 2002 with a radiological diagnosis of radial scar or complex sclerosing lesion confirmed on subsequent histopathology were included in this study. Patients were investigated with fine needle aspiration cytology then localisation biopsy (n=46) or straight to localisation biopsy (n=78). Patients where divided into two groups, one with pure RS/CSL with no associated epithelial features and the second with associated ADH, DCIS or invasive cancer., Results: One hundred and twenty-four lesions were confirmed histologically as radial scar or complex sclerosing lesions. The median age was 58 years. Of the 124 patients, 82 were pure RS/CSL. Forty-two had associated epithelial lesions, 22 patients had ADH and 20 patients had either in situ or invasive carcinoma. Where FNA was performed (n=46), mammograms had shown three lesions suspicious of cancer, which were not proven histologically. Mammograms picked up five malignancies out of the nine RS/CSL with associated cancers. Of these, FNA confirmed malignancy in only two patients. Where FNA was not done (n=78), mammogram had read five pure RS/CSL as cancers. It picked up only four cancers in RS lesions with DCIS/Ca out of 11., Conclusion: All screen-detected stellate lesions should be excised due to their association with pre-malignant and malignant conditions.

We examined breast cancer risk in association with overall glycemic index (GI), glycemic load (GL), and dietary carbohydrate and sugar intake in a prospective cohort of 49,613 Canadian women enrolled in the National Breast Screening Study who completed a self-administered food frequency questionnaire between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. During a mean follow-up of 16.6 years, we observed 1,461 incident breast cancer cases. GI, GL, total carbohydrate and total sugar intake were not associated with breast cancer risk in the total cohort. However, there was evidence of effect modification of the association between GI and breast cancer risk by menopausal status (p = 0.01), the hazard ratio for the highest versus the lowest quintile level of GI being 0.78 (95% CI = 0.52-1.16; ptrend = 0.12) in premenopausal women and 1.87 (95% CI = 1.18-2.97; ptrend = 0.01) in postmenopausal women. The associations between GI and GL were not modified by body mass index (BMI) or by vigorous physical activity among pre- or postmenopausal women. Similarly, the associations between GI/GL and risk in postmenopausal women were not modified by BMI, vigorous physical activity, or ever use of hormone replacement therapy (HRT), although the associations were slightly stronger among those who reported no vigorous physical activity (ptrend = 0.02), among those who reported ever using HRT (ptrend = 0.02) and among normal-weight women (BMI < 25 kg/m2; ptrend = 0.03). Our data suggest that consumption of diets with high GI values may be associated with increased risk of breast cancer among postmenopausal women, possibly more so among subgroups defined by participation in vigorous physical activity, ever use of HRT and those who are not overweight.

Background: Many studies of fruit and vegetable consumption showed inverse associations with breast cancer risk, suggesting the potential importance of carotenoids (and other phytochemicals) contained in these foods. To date, however, only one prospective cohort study has examined dietary carotenoids other than beta-carotene in relation to breast cancer risk., Objective: Our aim was to examine the relations between dietary intakes of beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, and lutein + zeaxanthin and breast cancer risk in a large cohort study of Canadian women., Design: A case-cohort analysis was undertaken in a cohort of 56 837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993 a total of 1589 women were diagnosed with biopsy-confirmed incident breast cancer. For comparison, a subcohort of 5681 women was randomly selected. After exclusions for various reasons, the analyses were based on 1452 cases and 5239 noncases., Results: We found no clear association between intakes of any of the studied carotenoids and breast cancer risk in the study population as a whole or in subgroups defined by smoking status; relative body weight (assessed by body mass index); intakes of total fat, energy, alcohol, or folic acid; family history of breast cancer; or menopausal status., Conclusions: Our data do not support any association between dietary intakes of the studied carotenoids and breast cancer risk. However, prospective cohort studies of carotenoids in relation to breast cancer are scarce and further studies are warranted.

Background: Sclerosing lobular hyperplasia presenting as a palpable, circumscribed nodular mass in a young female's breast is characterized histologically by prominent hyperplasia of the lobules and sclerosis of the intralobular connective tissue. The cytomorphologic features and differential diagnosis of the lesion are presented., Case: A 14-year-old female presented with a painless, progressively increasing, nodular, firm, mobile lump measuring 5 x 5 cm in the right breast. The clinical and radiologic diagnosis was fibroadenoma. Fine needle aspiration smears showed a clean background with uniform, round to oval epithelial cells in flat sheets, round clusters and rosettelike (acinar) arrangements. A few naked nuclei were present, while stromal fragments were not seen., Conclusion: When analyzed in the context of the clinical findings, the cytologic features of sclerosing lobular hyperplasia help to differentiate it from other benign palpable nodular lesions of the juvenile breast.

Available epidemiological evidence indicates that alcohol intake is associated with a higher risk of developing breast cancer. Plausible biological pathways include its effect on levels of estrogens, cell membrane integrity and cell-to-cell communication, inhibition of DNA repair, and congener effect. The present study evaluated the impact of alcohol on mortality from breast cancer, an area with relatively few studies in the literature. The subjects were participants in a Canadian prospective cohort study, the National Breast Screening Study (NBSS). Women were enrolled in the cohort from 1980 to 1985 to evaluate the efficacy of mammographic screening. Information on usual diet and alcohol intake at enrolment and other epidemiological variables was collected by means of a mailed, self-administered questionnaire. Mortality from breast cancer during follow- up to 31 December, 1993 was ascertained by record linkage to the Canadian Mortality Data Base maintained by Statistics Canada. During the follow-up period of 1980-1993 (average 10.3 years), 223 deaths from breast cancer were identified for this analysis. The hazard ratios for the risk of death from breast cancer increased with intakes of total alcohol of 10-20 g/day (1.039, 1.009-1.071) and > 20 g/day ( 1.063, 1.029-1.098). This increase was contributed largely by the intake of wine, a 15% increase in risk at intakes higher than 10 g/day of alcohol from wine. Alcohol from spirits was associated with a small decrease in risk of death (hazard ratio at 10g/day, 0.945, 0.915-0.976). The effect of alcohol from beer was not significant in the two categories studied. Although our results were statistically significant, the magnitude of the change in risk was small.

Objectives: To study the association between alcohol consumption and breast cancer risk., Methods: A case-cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 1469 women in the dietary cohort were diagnosed with biopsy-confirmed incident breast cancer. For comparative purposes a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons the analyses were based on 1336 cases and 5238 noncases., Results: When compared to nondrinkers the adjusted incidence rate ratios (95% confidence intervals) for those consuming > 0 and < or = 10 g of alcohol/day, > 10 and < or = 20 g/day, > 20 and < or = 30 g/day, > 30 and < or = 40 g/day, > 40 and < or = 50 g/day, and > 50 g/day were 1.01 (0.84-1.22), 1.16 (0.91-1.47), 1.27 (0.91-1.78), 0.77 (0.51-1.16), 1.00 (0.57-1.75), and 1.70 (0.97-2.98), respectively; the associated p value for the test for trend was 0.351. Similar findings were obtained when analyses were conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, for screen-detected and interval-detected breast cancer, and by levels of other breast cancer risk factors., Conclusions: The results of this study suggest that alcohol consumption might be associated with increased risk of breast cancer at relatively high levels of intake.

Histopathologic parameters were studied in fibroepithelial breast lesions comprising of Fibroadenomas (FAs), Juvenile cellular fibroadenomas (JCFs) as well as benign, borderline and malignant phyllodes tumours (B/Bo/MPTs). H & E stained sections of 67 cases (25 ICFA, 5 Mixed FA, 10 PCFA, 12 JCF and 15 PT) were retrieved from archival material and the microscopic features of each lesion, reviewed by two independent observers. A diagnosis was arrived at by consensus. Diagnostic criteria were laid down for each of the above lesions based on a statistical analysis of data obtained from a previously drawn up semiquantitative grading system for various stromal histomorphologic parameters. An increasing grade of stromal cellularity, pleomorphism, overgrowth and mitotic index was observed, from the benign to the borderline and overtly malignant lesions included in the spectrum. A semiquantitative grading of relevant stromal histomorphologic variables was found to be of immense diagnostic significance in fibroepithelial breast lesions and served to elucidate cases falling into the diagnostic grey zones of the spectrum.

The cytologic features of a case of adenoid cystic carcinoma of breast diagnosed on fine needle aspiration cytology (FNAC) in a 52 years old female are described. FNAC was carried out on outer quadrant of breast. The characteristic cytological features were numerous single to branching small round to Avoid cells at places forming microacini. Numerous pink hyaline globules of variable sizes were seen along with finger like projections containing basement membrane material.

Objective: To study the association between alcohol consumption and risk of benign proliferative epithelial disorders (BPED) of the breast (conditions which are thought to have premalignant potential)., Design: Case-cohort study., Setting: The study was undertaken within the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered dietary questionnaires. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 years at recruitment.), Subjects: The study subjects were the 657 women in the dietary cohort who were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 557 cases and 5028 non-cases., Results: When compared to non-drinkers, rate ratios (95% CI) for those consuming > 0 and < or =10 g of ethanol day(-1), >10 and < or =20 g day(-1), >20 and < or =30 g day(-1) and >30 g day(-1) were 0.35 (0.27-0.45), 0.26 (0.18-0.39), 0.29 (0.18-0.48), and 0.23 (0.13-0.40), respectively (the associated P value for the trend was 0.089). Similar findings were obtained from analyses conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, and for non-atypical and atypical forms of BPED, and there was little difference between the results for screen-detected and interval-detected BPED., Conclusions: Alcohol consumption was associated with a non-dose-dependent reduction in risk of BPED.

A case-cohort analysis of the association between diet and risk of benign proliferative epithelial disorders (BPED) of the breast was undertaken within a cohort of 56,537 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40 to 59 years.) BPED are thought to have premalignant potential. Specific hypotheses were that risk of BPED would increase with increasing energy-adjusted fat intake and decrease with increasing energy-adjusted vitamin A and fiber intake. Additionally, we explored the association between calcium intake and risk of BPED. During the active follow-up phase of the NBSS, 657 women in the dietary cohort were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a subcohort consisting of a random sample of 5,581 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 545 cases and 4,921 non-cases. Overall, the results were almost uniformly null, and provided little support for the study hypotheses. Rate ratios (95 percent confidence intervals [CI]) for the highest cf the lowest quintile levels for total fat, retinol, beta-carotene, fiber, and calcium were 0.88 (CI = 0.65-1.20), 0.97 (CI = 0.71-1.31), 0.94 (CI = 0.70-1.27), 1.11 (CI = 0.82-1.50), and 0.81 (CI = 0.60-1.07), respectively. There were too few cases of atypical BPED for meaningful analysis, but results for those whose BPED showed no atypia were similar to the overall results. Further analyses conducted separately in the screened and control arms of the NBSS also failed to provide strong support for dietary associations, as did those conducted separately for screen-detected and interval-detected BPED.

Nutritional factors have been suggested to play an important role in the prognosis of breast cancer through their effect on tumor characteristics. This study evaluated four tumor characteristics and prognosis in relation to premorbid diet and body size. From a cohort of 89,835 women in the National Breast Screening Study (NBSS) in Canada, data on 676 incident cases of invasive carcinoma of breast, on whom we had dietary information, were used. A high energy intake lowered the likelihood of being ER positive and PR positive but after adjusting for ER status, was still associated with a higher risk of dying of breast cancer. Total fat and various types of fats were associated with a greater likelihood that a woman would be ER and PR positive, however the likelihood of dying from breast cancer was higher with higher fat consumption. There was no significant effect of higher intakes of beta carotene or vitamin C on ER status, nodal status or tumor size, but a significantly lower risk of dying from breast cancer was observed. Higher intake of carbohydrates and calcium was associated with a lowered frequency of ER and PR positive status but also with a lower risk of dying. Of the five indicators of body size studied, higher triceps skinfold thickness was associated with a slightly lower chance of being ER positive, PR positive, and node negative, and a significantly higher likelihood of dying. It appears that while there are significant associations between some of the diet and body size variables and tumor characteristics, the effect of most nutritional factors on prognosis in breast cancer may not be mediated via their effect on tumor characteristics.

Obesity has been associated with poor prognosis of breast cancer, but studies investigating indicators of adiposity, independent of height, such as skinfold thickness and weight/height ratio, have been limited. From a cohort of 89,835 women in the National Breast Screening Study, data on histologically confirmed, incident cases of invasive carcinoma of breast, diagnosed between January 1981 to June 1992, were analyzed. Body measurements were taken at enrollment and other risk-factor information from a self-administered questionnaire completed prior to diagnosis of the breast cancer. Mortality data were obtained by linkage to Statistics Canada, provincial cancer registries, and annual follow-up of cases through physicians. Of the 5 measures of body size studied among cases, poor prognosis was associated with higher triceps skinfold thickness only. With every 5 mm increase in skinfold, the risk of dying increased approximately 12% (relative risk, 1.12; 95% confidence intervals, 1.01 to 1.24) in the 1033 cases examined and adjusted for age at diagnosis, number of positive axillary nodes involved, and body weight. Compared with women in the lowest quartile of skinfold thickness, women in the fourth quartile had a relative risk (RR) of 1.64 (95% CI, 0.99 to 2.73). None of the other measures--weight, height, body mass index or weight/height ratio--reached any statistical significance. Since the reliability and validity of skinfold measures used in our study were never established, and no data were available for changes in body size after diagnosis, the results of this study on skinfold thickness should be used only as indicative of a need for further studies.

Background: Consumption of a high-fat diet has been associated with poor survival in breast cancer patients. However, studies examining this association are limited and have not used adjustment of energy in their estimates., Purpose: The effect of usual diet before diagnosis of breast cancer on the risk of dying of breast cancer was examined in a cohort of women with breast cancer from the National Breast Screening Study (NBSS) in Canada., Methods: From a cohort of 89,835 women in the NBSS, a total of 1270 histologically confirmed cases of invasive carcinoma of the breast were identified by active follow-up, supplemented by passive follow-up involving record linkage to provincial cancer registries. Of these, 678 case patients who had completed a diet history and were diagnosed from January 1982 up to June 1992 formed the cohort for this investigation. Diet was ascertained from a self-administered diet-history questionnaire. Mortality data were obtained by linkage to the Canadian Mortality Data Base of Statistics Canada, provincial cancer registries, and annual follow-up of cases through physicians. Risk of dying and survival probabilities were estimated by the Cox proportional hazards method and the actuarial life-table method., Results: There were 83 deaths in this study cohort of 678 women; 76 deaths were due to breast cancer, and the remaining seven resulted from other causes. The 5-year survival rate was 90%. For every 5% increase in energy from saturated fat, the risk of dying of breast cancer increased by 50% (hazard ratio = 1.50; 95% confidence interval [CI]: 1.08-2.08). No significant increase in risk was seen with total fat intake (hazard ratio = 1.21; 95% CI = 0.91-1.61) or oleic acid intake (hazard ratio = 1.25; 95% CI = 0.90-1.74). There was a lower risk of dying of breast cancer in the highest quartiles of beta carotene intake (hazard ratio = 0.48; 95% CI = 0.23-0.99) and vitamin C intake (hazard ratio = 0.43; 95% CI: 0.21-0.86); both vitamins showed a significant dose-response relationship (P for trend, < or = .05). These effects varied with menopausal status at diagnosis and tumor characteristics., Conclusions: These results suggest an increased risk of dying of breast cancer with higher intakes of saturated fat before diagnosis and slightly reduced risk with higher intakes of beta carotene and vitamin C., Implications: More attention should be paid to premorbid dietary habits in relation to breast cancer prognosis. Further studies, however, need to be done with full ascertainment of dietary changes prior to and subsequent to diagnosis.

The association between alcohol consumption and breast cancer risk was examined in 519 newly incident, histologically confirmed cases of breast cancer diagnosed between 1982 and 1987 within a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a self-administered food frequency questionnaire including alcohol consumption at enrollment into the study prior to their breast cancer diagnosis. For the total cohort, only a weak association between total alcohol consumption and breast cancer risk is observed, the adjusted relative risk for those drinking 30 or more g/day being 1.22 (95% confidence interval (CI) 0.78-1.90) compared with nondrinkers. There is some evidence for a positive association in women who were premenopausal at the time of enrollment for whom there was a monotonic increase in risk with increasing alcohol intake. Compared with nondrinkers, the adjusted relative risk for alcohol consumption of between 0 and < 10 g of alcohol daily was 1.11 (95% CI 0.71-1.71), between 10 and < 20 g was 1.37 (95% CI 0.79-2.36), between 20 and < 30 g was 1.51 (95% CI 0.80-2.86), and > or = 30 g was 1.86 (95% CI 0.96-3.66; p (trend) = 0.07). These findings contrasted with the results for postmenopausal women where there appeared to be no evidence of any relation. The association in premenopausal women is generally reasonably consistent with that of other studies that have found positive associations with alcohol intake.

Risk of breast cancer was examined in relation to intake of dietary fiber and vitamins A, C, and E, and food groups which are sources of these dietary constituents, in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. Between 1982 and 1987, 519 incident, histologically confirmed cases of breast cancer were identified among women who previously had completed self-administered dietary questionnaires. Their nutrient and food intake was compared with that of 1,182 women who had not developed breast cancer during the follow-up period. Women at the uppermost quintile level of dietary fiber intake had a 30 percent reduction in risk of breast cancer relative to that for women at the lowest quintile level (adjusted odds ratio = 0.68, 95 percent confidence interval = 0.46-1.00), and the reduction in risk persisted after adjustment (separately) for total vitamin A, beta-carotene, vitamin C, and alpha-tocopherol. Inverse associations of similar magnitude were observed in association with consumption of pasta, cereals (the trend for which was statistically significant), and vegetables rich in vitamins A and C. Smaller, statistically nonsignificant reductions in risk were observed with increasing intake of dietary retinol, beta-carotene, and vitamin C, but the magnitude of these associations was reduced after adjustment for other dietary factors. Vitamin E intake was not associated with altered risk of breast cancer.

Between 1982 and 1987, 519 newly incident, histologically confirmed cases of breast cancer were identified in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a dietary questionnaire before the occurrence of their breast cancer, and this has been used to estimate their intake of dietary fat and several other nutrients. There is evidence of a positive association between breast cancer and total fat intake, with a relative risk of 1.35 (95% confidence interval, 1.00-1.82) per 77 g per day, and some evidence of a dose-response relationship (P = .052).

A case-control study has been conducted in four areas of Canada in which 400 cases of breast cancer matched by age and marital status with neighborhood controls were administered medical and dietary questionnaires. The study is suggestive of an increased risk of breast cancer in post-menopausal women with younger age at menarche and an increased risk with delay of age at natural menopause. No protective effect of early age at first pregnancy was demonstrated in either pre- or post-menopausal women. An increased frequency of pregnancies of four months duration or less was found in cases compared to controls and a greater frequency in pre-menopausal cases compared to controls of a history of irregular menstrual periods. In pre-menopausal women no association has been found between increased height and weight as risk factors for breast cancer. For post-menopausal women, however, a weak association with increased height has been found, while a strong association with increased weight both at the time of menopause and the 12 months preceding diagnosis has ben confirmed.

Three methods of estimating group and individual dietary consumption have been developed and assessed in a case-control study of diet and breast cancer. The methods comprised a 24-hour recall, a detailed quantitative diet history directed to the most recent two-month period and the two-month period six months before, and a four-day diet diary. There is a high degree of correlation between the estimates of food consumption for the controls using each of the methods. The highest estimate was obtained from the diet history, with a slightly higher estimate in the period six months before than the current period, while the lowest is found in the 24-hour recall. The latter corresponds with the same method in a Nutrition Canada Survey. It is concluded that all methods ara applicable to case-control studies, but the diet history is preferred when current food intake may be influenced by a disease.

A case-control study has been conducted in four areas in Canada in which 400 cases of breast cancer matched by age and marital status with neighborhood controls were administered a medical and dietary history questionnaire, a 24-hour recall for dietary information and a four-day diet record. The Study has produced evidence of an association between an increased intake of nutrients, especially total fat, in both pre-menopausal and post-menopausal women with breast cancer. Reasons why a weak association might have been anticipated are discussed, and it is concluded that in reality the association is stronger. Furthermore, its consistency with other evidence, both experimental and international, suggests that it is causal.