Risk Factors For Breast Carcinoma Research Articles

Association of Serum Vitamin D with Risk of Breast Carcinoma: An Observational Case-control Study from Western Maharashtra, India

Introduction: Breast carcinoma is one of the most prevalent types of carcinoma and the leading cause of death among all carcinomas. Recently, vitamin D deficiency has been reported as a risk factor for breast carcinoma. Vitamin D, as an anticarcinoma agent, prevents cellular differentiation, stimulates cell death, reduces angiogenesis, tumour progression, and metastasis. Aim: To investigate the relationship between vitamin D deficiency and the risk of breast carcinoma. Materials and Methods: An observational study was conducted at the Armed Forces Medical College, Pune, Maharashtra, India, between November 2018 and October 2020. A total of 57 cases diagnosed with breast carcinoma and 57 healthy controls were analysed. Physical and reproductive health parameters were compared, along with vitamin D status using student’s t-test and Mann-Whitney U test. Logistic regression was used to assess the risk of breast carcinoma. Results: Out of 114 women, 57 were cases and 57 were controls with a mean age of 52 vs 48 years. The mean value of serum vitamin D levels was significantly lower (19.45 vs 27.91 ng/mL, p<0.001) than controls. The percentage of serum Vitamin D deficiency was significantly higher in cases (28 (49.1%) vs 12 (21.1%), p<0.001) compared to controls. Vitamin D concentration <20 ng/mL was significantly associated with a higher risk of breast carcinoma (OR 10.8, 95% CI 3.1-37.6). Multiparity ≥3 was associated with a decreased risk of breast carcinoma (OR 2.250, 95% CI 0.599-8.447) compared to parity ≤2 (OR 3.241, 95% CI 0.916-11.466). In luminal A and triplenegative subtypes, severe vitamin D deficiency (<20 ng/mL) was observed (p=0.045) compared to other subtypes. Conclusion: The present study findings showed that women diagnosed with breast carcinoma had low vitamin D levels, which were linked to an increased risk and prognosis of breast carcinoma. Furthermore, multiparity lowers the risk of breast carcinoma.

Potential Risk Factors for Breast Carcinoma in Patients Presented in a Tertiary Care Hospital

Potential Risk Factors for Breast Carcinoma in Patients Presented in a Tertiary Care Hospital

Potential Risk Factors for Breast Carcinoma in Patients Presented in a Tertiary Care Hospital

Potential Risk Factors for Breast Carcinoma in Patients Presented in a Tertiary Care Hospital

Overexpression of HMGB3 and its prognostic value in breast cancer.

High mobility group protein B3 (HMGB3) is abundantly expressed in a number of malignancies, contributing to tumor cell growth and predicting poor outcomes. More research on the connection between HMGB3 and breast cancer is needed. The prognostic significance of HMGB3 in breast cancer was examined and validated in this study. Using The Cancer Genome Atlas (TCGA) database RNA sequencing and clinical data, we investigated the associations between HMGB3 expression and tumor mutations, prognosis, and immune infiltration in breast cancer. The Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), breast cancer gene-expression miner (bc-GenExMiner), UALCAN, OncoLnc, cBio Cancer Genomics Portal (cBioPortal), and LinkedOmics databases were applied to examine the levels of expression, mutation, coexpression, and immune correlation of HMGB3 in breast cancer. cBioPortal and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) were used for coexpression and enrichment analyses, respectively. Experimental tests and a separate cohort of breast cancer patients in our center were used for validation. To determine independent risk factors affecting breast carcinoma prognosis, multivariate Cox regression analysis was performed. The Kaplan-Meier method was applied to analyze the connection between HMGB3 expression and overall survival time in breast cancer. Pan-cancer investigation using the GEPIA and UALCAN databases revealed a high level of HMGB3 expression in different malignancies, including breast cancer. HMGB3 might be a potential diagnostic biomarker, according to the receiver operating characteristic (ROC) curve (AUC=0.932). And immunohistochemistry confirmed higher HMGB3 protein expression in breast cancer tissues in clinical samples. Experimental tests also showed that breast cancer cells have higher expression of HMGB3, and knockdown of HMGB3 can promote the proliferation of breast cancer cells and increase sensitivity to chemotherapy. Human epidermal growth factor receptor 2 (HER2), Nottingham Prognostic Index (NPI), basal-like status, nodal status (N+), triple-negative status, and Scarff-Bloom-Richardson (SBR) grade all showed positive correlations with HMGB3 expression. Conversely, HMGB3 expression was negatively associated with the expression of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer. Breast cancer patients with high HMGB3 expression had poor overall survival, which was validated by an analysis of a separate cohort of breast cancer patients in our center. Cox regression analysis identified high HMGB3 expression as an independently associated risk factor for breast carcinoma. The amount of immunological infiltration was substantially linked with the high expression of HMGB3. The chromosome centromeric region, ATPase activity, and the cell cycle are critical areas where HMGB3 is involved, according to enrichment analysis. Therefore, we suspected that HMGB3 might be a potential biomarker for detecting and treating breast carcinoma. Breast cancer tissues had higher HMGB3 expression than normal breast tissues. HMGB3 overexpression may serve as an indicator for poor breast cancer outcomes.

Abstract 1443: Environmental heavy metal toxicity and mammographic breast density in a Mississippi Delta southern state

Abstract Importance: Increased mammographic density (MD) is a strong independent risk factor for breast carcinoma. Ubiquitous environmental heavy metal (HM) exposure/toxicity appears pro-carcinogenic in several human cancers. However, studies in the current scientific literature have not elucidated specific connections between HM exposure and mammographically detected increases in breast density. Objective: To determine whether increases in heavy metals (ie, chromium, arsenic and cadmium) measured in urine as a biomarker for long-term exposure, associate with increased MD in a female study cohort in Arkansas. Design, Setting, Participants: One hundred thirty-nine participants in the Arkansas Rural Community Health (ARCH) study cohort, recruited through a mobile mammography unit at baseline, were included in this pilot study. Demographic/health history questionnaire data, urine, blood and saliva samples and incident mammograms classified by BI-RADS were ascertained after informed consent. Study protocol was approved by the Institutional Review Board at the University of Arkansas for Medical Sciences (UAMS). Main Outcome and Measures: Urinary chromium, arsenic and cadmium levels were determined using inductively coupled plasma mass spectrometry. The concentrations of HM were adjusted for urinary creatinine and specific gravity and the results categorized into tertiles. Multivariable logistic regression models were used to evaluate the association between HM exposure and MD. Association of both continuous and categorical variables were examined. Confounding variables in the multivariable models including age, race, BMI, age at menarche and smoking history were determined by a priori knowledge and statistical assessment. Results: Odds ratios (OR) and 95% confidence intervals (CI) for the association between each tertile of HM exposure and MD were used for the assessment. For the unadjusted model, increasing ORs for MD were noted with increased levels of both Chromium and Arsenic exposure. Increased ORs for MD were observed with increased levels of Chromium, Arsenic and Cadmium exposure in the multivariable adjusted model. However, none of these associations demonstrated statistical significance in this limited pilot study. Conclusion: Positive associations between HM exposure and MD were noted after adjusting for age, sex, BMI, age at menarche and smoking history in this pilot study. However, the association did not reach statistical significance at α = 0.05. Citation Format: Bobbie Dean Fine, Shelbie Stahr, Lora J. Rogers, Gail A. Runnells, Tung-Chin Chiang, Lihchyun J. Su. Environmental heavy metal toxicity and mammographic breast density in a Mississippi Delta southern state [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1443.

Evaluation of volumetric breast density as a risk factor for breast carcinoma in pre- and postmenopausal women, its association with hormone receptor status and breast carcinoma subtypes defined by histology and tumor markers

BackgroundMammographic breast density is acknowledged as an independent risk factor for breast cancer. Its association with different pathological types and tumors markers is still under evaluation. This study aims to assess the associations of volumetric density grades (VDG) with breast cancer risk in premenopausal and postmenopausal age groups separately. We also aim to assess the association of VDG with hormone receptor status and breast cancer subtypes defined by histology and tumor markers (ER, PR, Her 2-neu and Ki 67).ResultsThis retrospective study was done with inclusion of two comparable groups of 185 breast cancer cases and 244 healthy controls. These groups were further divided into pre‑ and postmenopausal subgroups. Mammograms of the cases and controls were evaluated by fully automated volumetric breast density software-VOLPARA and classified into four VDG. The hormone receptor status and breast cancer subtypes defined by histological features and tumor markers in the various VDG were also evaluated. The risk of developing carcinoma was significantly higher in women with high-density breasts (VDG-c + VDG-d) as compared with low-density breasts (VDG-a + VDG-b) in both premenopausal and postmenopausal subgroups. No significant difference was seen in the histopathological characteristics of breast cancer among various VDG.ConclusionsOur study suggests positive association between high VDG and risk of cancer in both premenopausal and postmenopausal group of Indian women. The hormone receptor status and breast cancer subtypes defined by histology and tumor markers did not reveal any relation to the grades of breast density.

Association of GSTP1 p.Ile105Val (rs1695, c.313A > G) Variant with the Risk of Breast Carcinoma among Egyptian Women.

Several reports examined the association of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant with the elevated risk of multiple cancerous diseases involving breast carcinoma, but with inconclusive findings. The primary purpose of this study is to test the association of this essential variant with the risk of breast carcinoma among Egyptian females. This case-control study was conducted based on 200 participants involving 100 women diagnosed with breast carcinoma and 100 unrelated cancer-free controls from the same district. The genomic DNA for all participants was genotyped utilizing T-ARMS-PCR procedure. The frequencies of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant indicated a statistically significant with the elevated risk of breast carcinoma under various genetic models, including allelic (OR = 2.48, P-value < 0.001) and dominant (OR = 2.36, P-value = 0.003) models. In conclusion, the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant was considered as an independent risk factor for breast carcinoma among Egyptian women.

Assessment of the Relationship between Obesity and Female Breast Carcinoma in Imamein Kadhumein Medical City

Background: Obesity, measured by body mass index (BMI), is a well-known danger feature for a widespreadvariation of illnesses. Yet, in breast carcinoma (B.Ca.) the link is a little discussed and differs according todifferent entities.Aims: This study aimed to assess the relationship between obesity and breast cancer in premenopausalwomen.Subjects and Method: This is a prospective study in which 800 women who were attending breast clinicin Al-Imamain Al-Kadhumain Medical City/Baghdad during the period from January 2016 to December2017 were followed up for the occurrence of BCa. of these, 50 women who developed BCa during thisperiod were selected to represent cases group. Other 50 age-matched women who did not have BCa wereselected to represent control group. General obesity (BMI) and central obesity (waist circumference (WC),hip circumference (HC) and waist/hip ratio (WHR)) were measured obtained from each patients either bydirect interview or from patient’s record.Results: Demographic, reproductive and laboratory data were comparable between the two groups.Stratification of BMI revealed significantly less cases having BMI &lt; 25 and more having BMI&gt;30 thancontrols. Moreover, cases showed significantly higher mean of WC (84.12±6.22 cm) than controls (77.6±7.18cm), Regarding hormonal receptor statuses, mean BMI (30.18± 9.21 kg/m2) was significantly higher inhormonal receptor negative cases compared to 26.31±9.1 kg/m2 in estrogen and progesterone receptorspositive with significant difference. Conclusions: These data shows that obesity is a possible risk factor forbreast carcinoma in premenopausal women.

Ovarian Carcinoma Occurring After Breast Carcinoma Detection of Risk Factors Using Bdort Test

Breast cancer is the most frequently diagnosed malignancy among women worldwide. There are many risk factors for breast carcinoma, such as genetics, Electro Magnetic Field Radiation (EMFs), the presence of human papillomaviruses (HPV), BRCA mutations, low vitamin D level, and toxins. The risk of developing ovarian metastases increases with the passage of time after the breast cancer diagnosis, and there are significant links between the tumor stage and the development of ovarian metastases (expressed Mammoglobin B). Because there is no screening test for ovarian cancer proven to be effective, women need to learn about their personal risk for developing ovarian cancer. This is especially true for the women already diagnosed with breast cancer, who should make sure if they are at risk for ovarian cancer. By using BiDigital O-Ring Test (BDORT), originated by Prof. Omura, we can detect a lot of risk factors contributing to the risk for ovarian cancer, such as the presence ofHPV in the ovary, exposure to EMFs, food intolerance, low level oftelomeres, the presence of Borrelia Burgdorferi (BB), Tuberculosis (TB) etc. A high level of HPV 16 in the ovary that is located on the same side as breast cancer could be detected, in addition to a high level of Integrin aSpl, as a marker of carcinogenesis. The cervix region infected by HPV is connected with the presence of HPV on both breasts, while the infection of one ovary (either left or right) is connected with the diseased breast (with cancer) on the same side. We examined 38 patients with confirmed diagnosis of breast cancer, by using indirect BDORT and in all patients we found out one ovary with a high level of HPV infection as with high level of Integrin aSpl . There are some mutual factors for the carcinogenesis of breast cancer and ovary cancer (HPV infection, BB, TB etc., toxins, EMFs). All patients reported being exposed to EMFs. 29 out ofa total of 38 (76.32%) patients had the infection of one ovary and the same side breast where exist breast carcinoma. In the same time on same side ovary we detected high level of HPV 16 and 18 and high level of Integrin aSpl. In three of38 patients we found out increased ovary tumor markers. In study group we found out 29 out ofa total of38 patients have a risk of ovary carcinoma. What we can learn from related literature is that ovarian carcinoma occurring after breast carcinoma is usually the metastasis of breast carcinoma; however, after this research, we believe that, in most cases, ovarian and breast carcinoma develop simultaneously, stimulated by the same or similar factors, and possibly by the same carcinoma stem cell.

A study on awareness about breast carcinoma and practice of breast self-examination among basic sciences' college students, Bengaluru.

Background:In India, the number of new breast cancer cases is about 115,000 per year and this is expected to rise to 250,000 new cases per year by 2015. It needs to be noted that breast cancer is leading in the age groups of 15–34 years which is a cause of concern as this denotes the need for educative and awareness programs targeting younger members of the society, to implement early practices of breast examination. This study was carried out with the intention of assessing the level of knowledge and awareness of carcinoma breast and breast self-examination (BSE) in female college students.Materials and Methods:This cross-sectional study was carried out in a well-known basic sciences college. After the pretest questionnaire was given, an awareness talk was given about breast cancer and BSE. A posttest questionnaire was administered. The data of pre- and post-test were collected and analyzed using SPSS.Results:Pretest and posttest were collected from 1030 students. The age of the study participants was ranged between 18 and 23 years. Most of them were aware of breast carcinoma, but half of them thought breast cancer affects the elderly. Regarding different aspects studied, 58% had a knowledge of at least one of the symptoms and 59% knew at least one of the risk factors for breast carcinoma. Only 185 (18%) women knew about BSE and 107 women practice it.Conclusions:This study concluded that the awareness of the breast cancer was good but the knowledge of signs and BSE was poor, which is utmost important for early detection and in reduction of mortality.

Evaluation of Common Risk Factors for Breast Carcinoma in Females: a Hospital Based Study in Karachi, Pakistan.

Breast malignancies are one of the leading causes of deaths in females worldwide. There are a number of risk factors associated with breast cancer but in Karachi Pakistan there are insufficient data available. A case control study was conducted on females in age group between 30-80 years. This study was accomplished by retrospective data collection in Aga Khan University Hospital Karachi, Pakistan. A total of 108 females with primary malignancy of breast were included along with 108 matched controls. Relationship of various factors with disease was studied using logistic regression to calculate odds ratios with 95 % confidence intervals. A total of 14 variables were analyzed and based on and 7 were found to be risk factors: old age, family history of breast cancer, family history of other carcinomas, personal history of breast carcinoma, early age of menarche, older age of mother at first delivery and lower number of children. Five factors, parity, breast feeding, history of oral contraceptive pills intake, past history of oophorectomy and hysterectomy showed protective associations. One variable, use of hormonal replacement therapy, showed a controversial link and one other, marital status, was not significant in this study. It is concluded that most of the well-known risk factors for breast cancer are also associated with the disease in the female population of Karachi, Pakistan. High risk patients should be the focus with the help of this study so that screening can be more effective for early diagnosis before clinically evident breast malignancy.

Descriptive study on selected risk factors and histopathology of breast carcinoma in a tertiary care centre in Kerala, India with special reference to women under 40 years old.

Breast cancer is the most common female cancer in Kerala, South India, with the incidence increasing in the past two decades, also in young women. However, there are limited data regarding the burden of disease, its epidemiology and histopathological characteristics in the state. This desciptive study covered 303 breast cancers evaluated during the period of December 2011 to August 2013 in the Department of Pathology, Government Medical College, Kottayam.The patients were also interviewed regarding selected risk factors. The majority of the cases were 41-60 years of age with a mean at presentation of 53 years. Infiltrating ductal carcinoma was the most common subtype, followed by pure mucinous carcinoma and then lobular carcinoma. Of the cases, 6.6% were nullipara and 52.8% had fewer than or equal to 2 children. Median age at first child birth was 23 years (national value-19.8 years). A significant proportion (15%) had family history of breast cancer. Some 13.5%(41 cases) comprised the young breast cancer group (≤40years) with a mean age at first child birth in them was 27.4 years, 5 being nullipara and 6 having a positive family history. Breast cancer awareness, better availability of screening techniques and identification and targeting high risk groups all help to tackle the increasing load of breast carcinoma. A good proportion of cases comprised the young breast cancer group (under 40). Younger women should thus also be educated about breast carcinoma-risk factors, symptoms and diagnostic techniques to help in early detection and effective approach esto treatment.

Meta-analysis of microsomal epoxide hydrolase gene polymorphism and the risk of breast carcinoma.

Carcinogenesis of breast carcinoma is very complicated. Previous studies have suggested conflicting results regarding the association between Tyr113His and His139Arg microsomal epoxide hydrolase (mEH) gene polymorphisms and risk of breast carcinoma. We conducted a meta-analysis to examine the relationship between these polymorphisms and breast carcinoma risk. We searched the PubMed, EMBASE, and Google Scholar databases to identify relevant studies. After extracting relevant data, the association between mEH polymorphisms and susceptibility to breast carcinoma was examined by meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. Seven studies were identified that included 6357 cases and 8090 controls. The mEH His-allele was not associated with the risk of breast carcinoma based on the allelic contrast model (OR = 0.99, 95%CI = 0.94-1.04, P = 0.58), dominant genetic model (OR = 1.14, 95%CI = 0.88-1.48, P = 0.33), or recessive genetic model (OR = 1.03, 95%CI = 0.96-1.10, P = 0.43). Similarly, the mEH Arg-allele was not associated with breast carcinoma risk based on the allelic contrast model (OR = 0.97, 95%CI = 0.91-1.04, P = 0.44), dominant genetic model (OR = 1.01, 95%CI = 0.84-1.21, P = 0.94), or recessive genetic model (OR = 1.04, 95%CI = 0.96-1.12, P = 0.35). Subgroup analysis based on ethnicity showed no association between the polymorphisms and risk of breast carcinoma. Thus, the Tyr113His and His139Arg mEH polymorphisms may not be risk factors for breast carcinoma.

Abstract SY21-02: Extracellular matrix density, alignment, and tumor progression

Abstract An increase in the mammographic density of breast tissue is correlated to a four to six-fold increased risk of developing breast carcinoma, making it the single biggest risk factor for breast carcinoma. Increased breast density is associated with a significant increase in the deposition of ECM components, most notably collagen, which leads to an increase in matrix stiffness. In a mouse model of increased collagen deposition, we find that mammary tumor incidence, invasion, and metastasis increased three-fold. Mammary tumors arising in FAK-/- mammary glands were non-invasive and non-metastatic. Gene expression profiling of these tumors identified a metastasis signature regulated by FAK, and further identify novel mechanisms and signaling pathways governing invasion into collagen matrices. Using state-of-the-art non-linear optical imaging techniques (FLIM and SHG), we have imaged collagen and cells at the tumor-stromal boundary in live, unfixed mammary tumors. We find that during tumor progression, the structure and alignment of collagen fibers is altered, such that the perpendicular realignment of collagen fibers is completely coincident with areas of local invasion. A recent analysis of 207 human samples demonstrates that the presence of perpendicular aligned collagen was a novel significant and independent prognostic indicator of poor patient survival, with a risk factor of 4.3. To determine whether fibril alignment facilitates invasion, we engineered aligned matrices, and found that human breast carcinoma cells preferentially invaded along perpendicularly aligned vs. random or parallel collagen fibers. Our results demonstrate collagen fibers serve as a highway to facilitate local invasion, and promote distal metastasis. Citation Format: Patricia J. Keely. Extracellular matrix density, alignment, and tumor progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr SY21-02. doi:10.1158/1538-7445.AM2014-SY21-02

Long-term use of metformin and the molecular subtype in invasive breast carcinoma patients - a retrospective study of clinical and tumor characteristics.

BackgroundMetformin may exhibit inhibitory effects on cancer cells by inhibiting mTOR signaling pathway. The aim of our retrospective study was to examine if patients with breast carcinoma (BC) and diabetes mellitus (DM) receiving metformin have a lower stage of carcinoma in comparison to patients not receiving metformin, and if the use of metformin correlates with the molecular subtype of BC.MethodsA chart review of 253 patients with invasive BC and DM (128 on metformin and 125 not on metformin) was performed. Control group consisted of 320 consecutive patients with invasive BC without DM. BC subtypes were classified by immunohistochemical surrogates as luminal A (estrogen receptor [ER] + and/or progesterone receptor [PR]+, HER-2-), luminal B (ER + and/or PR+, HER-2+), HER-2 (ER-, PR-, HER-2+), triple-negative/basal (ER-, PR-, HER-2-).ResultsPatients on metformin had a lower proportion of T3 or T4 tumors than patients who were not receiving metformin (16% vs. 26%; p = 0.035). No statistical difference was found between the two study groups in N stage. Patients with DM on metformin, with DM not on metformin and the control group had different molecular subtypes of BC (p = 0.01): the luminal A subtype was found in 78%, 83% and 71%, the luminal B in 12.6%, 9% and 11%, HER-2 in 0.8%, 1.6% and 8%, and the triple-negative/basal-like subtype in 8.6%, 6.4% and 10%, respectively.ConclusionOur data indicate that long-term use of metformin use correlates with molecular subtype of BC in diabetics on metformin in comparison to diabetics not on metformin and patients without DM. However, most likely, different distribution of the molecular subtypes of BC in these three groups of patients was caused by other risk factors for breast carcinoma, such as age of patients or obesity.

Polymorphism of the glutathione S-transferase P1 gene (GST-pi) in breast carcinoma.

Breast carcinoma is the most common cancer and cause of death among females worldwide, including Jordan. The risk factors for breast carcinoma are linked to DNA mutation and failure of DNA repair or detoxification systems. Identification of susceptibility factors that predispose individuals to breast carcinoma if they are exposed to particular environmental agents might give further insight into the etiology of this malignancy. The glutathione S-transferase (GST) enzyme family detoxifies carcinogenic compounds. Several genes that code for these enzymes are polymorphic, with particular genotypes previously shown to confer an increased carcinoma risk. The present study investigates GST-pi polymorphism in 100-tissue samples previously diagnosed as breast carcinoma, and in 48 non-cancer age-matched breast tissues, using the restriction fragment length polymorphism (RFLP) method for the polymerase chain reaction (PCR) product. Among breast cancer cases, 58%, 40% and 2% were homozygous (Ile/Ile), heterozygous (Ile/Val) and homozygous (Val/Val) respectively. In the control group, 58%, 37.5% and 4.2% were homozygous (Ile/Ile), heterozygous (Ile/Val), and homozygous (Val/Val) respectively. Our results did not support the involvement of GST-pi gene polymorphism in susceptibility to breast carcinoma in the tested North Jordanian female population.

Lobular neoplasia on core needle biopsy does not require excision

Lobular neoplasia (LN), encompassing atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), is often an incidental finding on core needle biopsies (CNBs) performed in instances of radiologic densities and/or calcifications. Because LN is generally considered a risk factor for breast carcinoma, the utility of subsequent excision is controversial. The authors' database yielded 98 cases of LCIS and/or ALH. Cases containing LN accompanied by a second lesion mandating excision (eg, radial scar, atypical ductal hyperplasia [ADH]) and those failing to meet strict diagnostic criteria for LN (eg, atypical cells, mitoses, single-cell necrosis) were excluded. Radiographic calcifications were correlated with their histologic counterparts in terms of size, number, and pattern. Ninety-one biopsies were performed for calcifications and 7 were performed for mass lesions. The ages of the patients ranged from 35 to 82 years. Fifty-three patients were followed radiologically without excision, 42 of whom had available clinicoradiologic information. The 45 patients who underwent excision were without disease at follow-up periods ranging from 1 to 8 years. Of these 45 patients, 42 (93%) had biopsy results demonstrating only LN. The remaining 3 patients had biopsies with the following findings: ADH in 1 biopsy, residual LCIS and a separate minute focus of infiltrating lobular carcinoma (clearly an incidental finding) in the second biopsy, and ductal carcinoma in situ admixed with LCIS in the third biopsy (a retrospective examination performed by 2 blinded breast pathologists revealed foci of atypical cells and mitoses). Excision of LN is unnecessary provided that: 1) careful radiographic-pathologic correlation is performed; and 2) strict histologic criteria are adhered to when making the diagnosis. Close radiologic and clinical follow-up is adequate.

Risk factors for breast carcinoma in situ versus invasive breast cancer in a prospective study of pre- and post-menopausal women

Risk factors for breast carcinoma in situ and invasive breast cancer were compared using data from 61,844 women (61% post-menopausal) with no prior breast cancer and at least one screening mammogram between April 1, 1996 and June 30, 2001. The women were followed until a subsequent mammogram before July 1, 2001, or a benign biopsy or breast cancer diagnosis before June 30, 2002. A total of 1,191 breast cancers (300 in situ and 891 invasive) were diagnosed during an average follow-up of 3.1 years. Multivariate Cox regression models were used to estimate the relative risks (RR) of in situ and invasive cancer associated with family history of breast cancer, age at first childbirth or nulliparity, post-menopausal hormone use, body mass index (BMI), and mammographic breast density. Separate analyses were done for pre- and post-menopausal women. BMI was unrelated to risk of in situ cancer regardless of menopausal status, but was associated with an increased risk of invasive cancer in post-menopausal women (RR = 1.9 for BMI > or = 30 vs. BMI < 22, 95% confidence interval 1.4-2.5). Later childbearing and nulliparity were more strongly associated with in situ than invasive cancer in pre-menopausal women. Post-menopausal hormone use was more strongly associated with invasive disease. RR associated with family history and breast density were similar for in situ cancer and invasive cancer. Results indicating that BMI is related to post-menopausal invasive cancers but unrelated to in situ cancers are consistent with the hypothesis that concomitants of obesity activate proliferation.

The Breast: Comprehensive Management of Benign and Malignant Diseases

The Breast: Comprehensive Management of Benign and Malignant Diseases

DNA repair and breast carcinoma susceptibility in women.

Breast carcinoma is the most common cancer and the second leading cause of cancer-related deaths among women. The disease represents approximately 31% of all cancers in Puerto Rican women. Several DNA repair pathways are involved in preventing carcinogenesis. The current study evaluated the hypothesis that a reduced DNA repair capacity (DRC) is a susceptibility factor for breast carcinoma. A retrospective case-control clinical study was performed to compare age-matched DRC in 33 women with histopathologically confirmed breast carcinoma (cases) and 47 cancer-free women (controls). DRC was measured using a host cell reactivation assay with a luciferase reporter gene and then transfected into human peripheral lymphocytes. A questionnaire was used to solicit breast carcinoma risk factors. Women with breast carcinoma had a mean DRC of 5.6% +/- 0.5 standard error of the mean (SEM). Cancer cases had a 36% reduction (P<0.001) in DRC when compared with the control group (DRC=8.7% +/- 0.7 SEM). Younger participants with breast carcinoma were found to have a more significant reduction in DRC when compared with age-matched controls. Family (odds ratio [OR]=4.1), maternal lineage (OR=5.5), and maternal (OR=12.4) history of breast carcinoma were found to be the only statistically significant (P<0.05) risk factors associated with the disease. The findings supported the hypothesis that a low DRC is a susceptibility factor for breast carcinoma. A 1% decrease in DRC corresponded to a 22% increase in breast carcinoma risk. To the authors' knowledge, the current study was the first to directly determine the DRC of women with breast carcinoma. Because DRC is an independent risk factor for breast carcinoma, the DRC of women may be a useful marker in predicting susceptibility.