Obesity has been associated with increased mortality from hormone dependant cancers such as breast cancer which is the most prevalent cancer in women. The link between obesity and breast cancer can be attributed to excess estrogen produced through aromatization in adipose tissue. The role of steroid hormone receptors in breast cancer development is well studied but how obesity can affect the expression pattern of steroid hormones in patients with different grades of breast cancer was the aim of this study.
In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI < 25 kg/m2 and 34 obese, BMI ≥ 25 kg/m2). The mean age of participants was 44.53 ± 1.79 yr (21–70 yr). The serum level of estrogen, progesterone and androgen determined by ELISA. Following quantitative expression of steroid hormone receptors mRNA in tumor tissues evaluated by Real-time PCR. Patients with previous history of radiotherapy or chemotherapy were excluded. SPSS 16 was used for data analysis and P < 0.05 considered statistically significant.
The difference in ERα, ERβ and PR mRNA level between normal and obese patients was significant (P < 0.001). In addition, the expression of AR mRNA was found to be higher than other steroid receptors. There was no significant relation between ERβ gene expression in two groups (P = 0.68). We observed a significant relationship between ERα and AR mRNA with tumor stage and tumor grade, respectively (P = 0.023, P = 0.015).
According to the obtained results, it is speculated that obesity could paly a significant role in estrogen receptors gene expression and also could affect progression and proliferation of breast cancer cells.
obesity; breast cancer; steroid receptors; steroid hormones
Exemestane is an irreversible inhibitor of the aromatase enzyme, which is a key component in the production of estrogen. The majority of breast cancers are sensitive to the proliferative effects of estrogen. Exemestane is approved for the adjuvant treatment of postmenopausal women with breast cancer after 2 to 3 years of tamoxifen therapy, based on a 32% improvement in disease-free survival compared with 5 years of tamoxifen alone (P < 0.001). Exemestane has also shown clinical benefits as an upfront therapy. The safety profile of exemestane shares some side effects with tamoxifen (hot flashes and arthralgia), but is not associated with an increased risk of endometrial cancer or thromboembolic events. This review will discuss in detail the efficacy and safety of exemestane in early breast cancer.
aromatase inhibitor; breast cancer; exemestane; disease-free survival; tamoxifen
BRCA1 is a tumor suppressor protein involved in maintaining genomic integrity through multiple functions in DNA damage repair, transcriptional regulation, cell cycle checkpoint, and protein ubiquitination. The BRCA1-BARD1 RING complex has an E3 ubiquitin ligase function that plays essential roles in response to DNA damage repair. BRCA1-associated cancers have been shown to confer a hypersensitivity to chemotherapeutic agents. Here, we have studied the functional consequence of the in vitro E3 ubiquitin ligase activity and cisplatin sensitivity of the missense mutation D67Y BRCA1 RING domain. The D67Y BRCA1 RING domain protein exhibited the reduced ubiquitination function, and was more susceptible to the drug than the D67E or wild-type BRCA1 RING domain protein. This evidence emphasized the potential of using the BRCA1 dysfunction as an important determinant of chemotherapy responses in breast cancer.
BRCA1; cisplatin; ubiquitination; cancer chemotherapy
Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date.
triple-negative breast cancer; basal-like; targeted therapy
Endoplasmic reticulum calcium homeostasis is involved in several essential cell functions including cell proliferation, protein synthesis, stress responses or secretion. Calcium uptake into the endoplasmic reticulum is performed by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). In order to study endoplasmic reticulum calcium homeostasis in situ in mammary tissue, in this work SERCA3 expression was investigated in normal breast and in its benign and malignant lesions in function of the cell type, degree of malignancy, and histological and molecular parameters of the tumors. Our data indicate, that although normal breast acinar epithelial cells express SERCA3 abundantly, its expression is strongly decreased already in very early non-malignant epithelial lesions such as adenosis, and remains low in lobular carcinomas. Whereas normal duct epithelium expresses significant amounts of SERCA3, its expression is decreased in several benign ductal lesions, as well as in ductal adenocarcinoma. The loss of SERCA3 expression is correlated with Elston-Ellis grade, negative hormone receptor expression or triple negative status in ductal carcinomas. The concordance between decreased SERCA3 expression and several histological, as well as molecular markers of ductal carcinogenesis indicates that endoplasmic reticulum calcium homeostasis is remodeled during tumorigenesis in the breast epithelium.
breast cancer; calcium signaling; endoplasmic reticulum; SERCA; calcium pump; ion transport
Delphinidin is a polyphenolic compound found in many brightly colored fruits and vegetables. Delphinidin is also the major bioactive component found in many dietary supplements that are currently consumed as complementary cancer medicine including pomegranate extract. The purpose of the current study was to determine the in vitro biological effects of delphinidin on established breast cancer cell lines of varying molecular subtypes in comparison to non-transformed breast epithelial cells. We examined cell proliferation, apoptosis, and growth inhibition in response to delphinidin using a tetrazolium salt-based assay, DNA fragmentation assay, and anchorage-independent growth assay. In comparison to vehicle control, delphinidin inhibited proliferation (P < 0.05), blocked anchorage-independent growth (P < 0.05), and induced apoptosis (P < 0.05) of ER-positive, triple negative, and HER2-overexpressing breast cancer cell lines with limited toxicity to non-transformed breast epithelial cells. MAPK signaling was partially reduced in triple negative cells and ER-negative chemically transformed MCF10A cells after treatment with delphinidin. In addition, delphinidin induced a significant level of apoptosis in HER2-overexpressing cells in association with reduced HER2 and MAPK signaling. Since delphinidin is often consumed as a complementary cancer medicine, the effect of delphinidin on response to specific HER2-targeted breast cancer therapies was examined by proliferation assay. Results of these drug combination studies suggested potential antagonism between delphinidin and HER2-directed treatments. In summary, the data presented here suggest that single agent delphinidin exhibits growth inhibitory activity in breast cancer cells of various molecular subtypes, but raise concerns regarding potential drug antagonism when used in combination with existing targeted therapies in HER2-overexpressing breast cancer.
breast cancer; delphinidin; HER2; erbB2; triple negative
GP88 (PC-Cell Derived Growth Factor, progranulin) is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC) and healthy volunteers (HV).
An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay.
Serum GP88 level was 28.7 + 5.8 ng/ml in HV and increased to 40.7 + 16.0 ng/ml (P = 0.007) for stage 1–3 and 45.3 + 23.3 ng/ml (P = 0.0007) for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression.
These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.
progranulin; GP88; breast cancer; biomarker
In this study we evaluate the influence of subject pose during image acquisition on quantitative analysis of breast morphology. Three (3D) and two-dimensional (2D) images of the torso of 12 female subjects in two different poses; (1) hands-on-hip (HH) and (2) hands-down (HD) were obtained. In order to quantify the effect of pose, we introduce a new measure; the 3D pBRA (Percentage Breast Retraction Assessment) index, and validate its use against the 2D pBRA index. Our data suggests that the 3D pBRA index is linearly correlated with the 2D counterpart for both of the poses, and is independent of the localization of fiducial points within a tolerance limit of 7 mm. The quantitative assessment of 3D asymmetry was found to be invariant of subject pose. This study further corroborates the advantages of 3D stereophotogrammetry over 2D photography. Problems with pose that are inherent in 2D photographs are avoided and fiducial point identification is made easier by being able to panoramically rotate the 3D surface enabling views from any desired angle.
three-dimensional; stereophotogrammetry; subject pose; validation; breast; symmetry; surgical planning; pBRA
In the US there are over 2.5 million breast cancer survivors (BCSs), most of whom have required some type of intensive treatment. How individuals cope with the treatment process may relate to why neurocognitive problems arise.
We explored the impact of treatment for breast cancer (BC) on performance of the Memory Island task, both on working memory and on the general index of cognitive performance in relation to coping strategies of BCSs compared to age-matched controls.
The evidence obtained suggests a reduced performance in visuospatial memory in BCSs. Those who used emotional coping strategies displayed reduced performance in visuospatial learning and immediate memory. Those women who used problem-focused coping strategies performed better in those tasks measuring psychomotor speed, general intelligence, and delayed visuospatial memory.
It is concluded that further investigation of the relationship between coping strategies and performance on visuospatial tasks may provide useful information on residual levels of neurocognitive deficits and psychosocial adaptation in BCSs.
breast cancer survivors; Puerto Rican; emotion-focused; problem-focused; visuospatial memory; Memory Island
Breast cancer is the most common cancer among Egyptian women. We report the unique assessment of hope and social support outcomes of women with breast cancer after mastectomy in Egyptian community.
Patients and methods:
Between July 2009 and June 2010, three hundred and one women with newly diagnosed breast cancer joined this study. Socio-demographic data including patient’s age, level of education, occupation, social status, and residence were collected by means of structured interviews based on special questionnaires. These questionnaires were designed to measure hope and social support.
Age ranged from 21 to 88 years (median = 45.8 years and SD ± 13.3). A low degree of hope was reported in 103 patients (34.2%), a moderate degree in 109 patients (36.2%), and a high degree in 89 patients (29.6%). A low degree of social support was reported in 119 patients (39.5%), a moderate degree in 101 patients (33.6%), and a high degree in 81 patients (26.9%).
Social support is related to many psychological factors, which can be quantitatively analyzed and it can predict hope. However, there were no significant differences between the socio-demographic variables (age, educational levels, residence and martial status) and social support, hope, and their sub-components among Egyptian women with breast cancer.
breast cancer; social support; hope; mastectomy
Ipsilateral breast tumor recurrence (IBTR) is an increasingly common clinical challenge. IBTRs include True Recurrences (TR; persistent disease) and New Primaries (NP; de novo tumors), but discrimination between these is difficult. We assessed tumor infiltrating leukocytes (TIL) as biomarkers for distinguishing these types of IBTR using primary tumors and matched IBTRs from 24 breast cancer patients, half of which were identified as putative TRs and half as NPs using a previously reported clinical algorithm. Intratumoral lymphocyte populations (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) and macrophages (CD68) were quantified by immunohistochemistry in each tumor. Compared to matched primaries, TRs showed significant trends towards increased CD3+ and CD8+ TIL, while these populations were often diminished in NPs. Comparison of IBTRs showed that TRs had significantly higher levels of CD3+ (P = 0.0136), CD8+ (P = 0.0092), and CD25+ (P = 0.0159) TIL than NPs. We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.
breast cancer; ipsilateral breast tumor recurrence; true recurrence; new primary; immune response; tumor infiltrating leukocytes
Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers.
Patients and methods:
We organized an analytic cross-sectional study of 105 women diagnosed with breast cancer who have been operated on between 2008 to 2010. We evaluated age, size, hormone receptor status, HER-2 and P53 expression as possible indicator of lymph node involvement.
There is a direct correlation between positive progesterone receptor status and being younger than 40 (P < 0.05). Also, compared with older women, young women had tumors that were more likely to be large in size and have higher stages (P < 0.05). Furthermore patients with negative progesterone receptor status were more likely to have HER-2 overexpression (P < 0.05). The differences in propensity to lymph node metastasis between hormone receptor statuses were not statically significant.
Although negative progesterone receptor tumors were more likely to have HER-2 overexpression, it is possible that higher stage and larger size breast cancer in younger women is related to positive progesterone receptor status.
breast cancer; estrogen receptor; progesterone receptor; lymph node metastasis; age
We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.
invasion; cell adhesion; cell aggregation; breast tumor cell inhibition; tumor imaging
Basal-like breast cancer has been reported to be the most aggressive and deadly carcinoma sub-type. Patients diagnosed with this subtype have a less than 50% five-year survival. In addition, many studies have reported that this sub-type is more prevalent in specific ethnic groups and is believed to be a key factor that drives certain ethnic disparities in mortality. In order to effectively study this sub-type and determine unique gene expression and biochemical pathways which sustain this cancer’s growth, we sought to identify human breast cancer cell lines that represent a model for the basal-like subtype. Here, we report our findings which indicate the African American cell line CRL-2335 is a true representative of basal-like breast carcinoma.
basal-like breast cancer; cell line model; triple negative breast cancer
Taxanes are highly active chemotherapeutic agents in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-paclitaxel is a solvent free, albumin-bound 130-nanometer particle formulation of paclitaxel (Abraxane®, Abraxis Bioscience), which was developed to avoid toxicities of the Cremophor vehicle used in solvent-based paclitaxel. In a phase III clinical trial, nab-paclitaxel demonstrated higher response rates, better safety and side-effect profile compared to conventional paclitaxel, and improved survival in patients receiving it as second line therapy. Higher doses can be administered over a shorter infusion time without the need for special infusion sets or pre-medications. It is now approved in the US for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, where prior therapy included an anthracycline. Recently, several phase II studies have suggested a role for nab-paclitaxel as a single agent and in combination with other agents for first-line treatment of metastatic breast cancer.
nab-paclitaxel; nab-technology; paclitaxel; metastatic breast cancer; taxanes
To compare breast volume measurement techniques in terms of accuracy, convenience, and cost.
Breast volumes of 30 patients who were scheduled to undergo total mastectomy surgery were measured preoperatively by using five different methods (mammography, anatomic [anthropometric], thermoplastic casting, the Archimedes procedure, and the Grossman-Roudner device). Specimen volume after total mastectomy was measured in each patient with the water displacement method (Archimedes). The results were compared statistically with the values obtained by the five different methods.
The mean mastectomy specimen volume was 623.5 (range 150–1490) mL. The breast volume values were established to be 615.7 mL (r = 0.997) with the mammographic method, 645.4 mL (r = 0.975) with the anthropometric method, 565.8 mL (r = 0.934) with the Grossman-Roudner device, 583.2 mL (r = 0.989) with the Archimedes procedure, and 544.7 mL (r = 0.94) with the casting technique. Examination of r values revealed that the most accurate method was mammography for all volume ranges, followed by the Archimedes method.
The present study demonstrated that the most accurate method of breast volume measurement is mammography, followed by the Archimedes method. However, when patient comfort, ease of application, and cost were taken into consideration, the Grossman-Roudner device and anatomic measurement were relatively less expensive, and easier methods with an acceptable degree of accuracy.
breast density; mammography-negativity; macromastia; oncoplastic surgery; reduction mammaplasty
Proteomics is a highly informative approach to analyze cancer-associated transformation in tissues. The main challenge to use a tissue for proteomics studies is the small sample size and difficulties to extract and preserve proteins. The choice of a buffer compatible with proteomics applications is also a challenge. Here we describe a protocol optimized for the most efficient extraction of proteins from the human breast tissue in a buffer compatible with two-dimensional gel electrophoresis (2D-GE). This protocol is based on mechanically assisted disintegration of tissues directly in the 2D-GE buffer. Our method is simple, robust and easy to apply in clinical practice. We demonstrate high quality of separation of proteins prepared according to the reported here protocol.
2D-GE; breast tissue; sample preparation; SBO4 buffer
Expression of human telomerase reverse transcriptase (hTERT) occurs in most cancers but its relation with obesity is unclear. This study explores the association between leptin levels and anthropometric indices with hTERT mRNA levels in breast cancer patients of different obesity grades.
Materials and methods:
In this case-control study, 65 breast cancer patients participated. Expression of tissues hTERT mRNA was carried out by real-time reverse transcription polymerase chain reaction. Leptin concentrations were measured by enzyme-linked immunoassay.
Twelve patients (18.46%) were hTERT negative and 53(81.54%) were positive. hTERT mRNA levels were associated with BMI but not with waist circumference (WC) (r = 0.219, P = 0.22) and waist to hip ratio (WHR) (r = 0.212, P = 0.237). Leptin level and hTERT mRNA levels (r = 0.484, P = 0.008) were correlated as well as BMI and hTERT expression.
This study has shown a correlation between leptin levels and hTERT expression. These findings may clarify the role of leptin in breast carcinogenesis, and hence obesity could be responsible for increased incidences in breast cancer as well as its progression via enhanced production of leptin.
breast cancer; obesity; adipokienes
The objective of this study was to determine if measurements of breast morphology computed from three-dimensional (3D) stereophotogrammetry are equivalent to traditional anthropometric measurements obtained directly on a subject using a tape measure. 3D torso images of 23 women ranged in age from 36 to 63 who underwent or were scheduled for breast reconstruction surgery were obtained using a 3dMD torso system (3Q Technologies Inc., Atlanta, GA). Two different types (contoured and line-of-sight distances) of a total of nine distances were computed from 3D images of each participant. Each participant was photographed twice, first without fiducial points marked (referred to as unmarked image) and second with fiducial points marked prior to imaging (referred to as marked image). Stereophotogrammetry was compared to traditional direct anthropometry, in which measurements were taken with a tape measure on participants. Three statistical analyses were used to evaluate the agreement between stereophotogrammetry and direct anthropometry. Seven out of nine distances showed excellent agreement between stereophotogrammetry and direct anthropometry (both marked and unmarked images). In addition, stereophotogrammetry from the unmarked image was equivalent to that of the marked image (both line-of-sight and contoured distances). A lower level of agreement was observed for some measures because of difficulty in localizing more vaguely defined fiducial points, such as lowest visible point of breast mound, and inability of the imaging system in capturing areas obscured by the breast, such as the inframammary fold. Stereophotogrammetry from 3D images obtained from the 3dMD torso system is effective for quantifying breast morphology. Tools for surgical planning and evaluation based on stereophotogrammetry have the potential to improve breast surgery outcomes.
three-dimensional; anthropometry; validation; breast; photogrammetry; stereophotogrammetry; surgical planning
Breast Cancer is the most prevalent cancer in the world with 4.4 million survivors up to 5 years following the diagnosis.1 In the US alone approximately forty thousand women die annually of metastatic breast cancer (MBC). Despite many effective systemic treatment options approximately 50% of women with MBC succumb to the disease within 24 months of the diagnosis.2 Ixabepilone is a novel, first in class member of the epothilone class of antineoplastic agents. Ixabepilone is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and Capecitabine. Ixabepilone is also indicated in combination with Capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Ixabepilone was extensively studied as a single agent in patients with MBC and was found to be effective and well tolerated with a predictable and manageable safety profile. Not surprisingly prior exposure to anthracyclines and taxanes affects significantly the potential for response to therapy with single agent Ixabepilone in metastatic setting. MBC patients with taxane resistant MBC have objective response rate (RR) of 12%, patients with prior low exposure to taxanes and/or resistance RR = 22%, Ixabepilone treatment after adjuvant anthracycline therapy exposure renders RR = 42% and in Taxane naïve patients RR = 57%. In two large phase III studies of Ixabepilone + Capecitabine versus Capecitabine alone, progression free survival (PFS) and overall response rates (RR) were higher in the combination treatment arms, but no survival advantage was seen overall. Treatment with Ixabepilone + Capecitabine in a phase II study resulted in an overall response rate (ORR) of 23% in ER/PR/HER2 negative, triple-negative breast cancer patients (TNBC) while ORR of 31% was seen in a preplanned pooled analysis of TNBC in the phase III trials of Ixabepilone + Capecitabine. Significantly prolonged median PFS was seen for TNBC treated with the combination of Ixabepilone + Capecitabine compared to Capecitabine alone 4.2 vs. 1.7 months respectively. Ixabepilone as single agent appears to show excellent antitumor activity in patients with TNBC MBC. Addition of Ixabepilone to Capecitabine results in approximately doubling in median PFS for TNBC versus Capecitabine alone. Single agent Ixabepilone is generally well tolerated, and its toxicity profile does not overlap with that of Capecitabine and therefore depending on prior exposure to chemotherapy both single agent Ixabepilone or in combination with Capecitabine can be used safely and effectively for treatment of advanced breast cancer.
Ixabepilone; metastatic breast cancer; monotherapy; in combination with capecitabine; triple negative breast cancer
Both indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism. The major trial objective was to determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation. Higher concentrations of C-2 metabolites and lower concentrations of C-16 metabolites may reduce breast cancer risk and risk for other hormonally-related cancers.
Forty-seven pre-menopausal and forty-nine post-menopausal women were recruited for this study, and were divided by random allocation into treatment and placebo group. The treatment supplement contained HMR lignan, indole-3-carbinol, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle, and each woman consumed either treatment or placebo for 28 days. At day 0 and day 28, blood samples were analysed for serum enterolactone concentrations, and first morning random urine samples were assessed for estrogen metabolites. Repeated measures ANOVA statistical testing was performed.
In pre-menopausal women, treatment supplementation resulted in a significant increase (P < 0.05) in urinary 2-OHE concentrations and in the 2:16α-OHE ratio. In post-menopausal women, treatment supplementation resulted in a significant increase in urinary 2-OHE concentrations. In pre- and post-menopausal women combined, treatment supplementation produced a significant increase in urinary 2-OHE concentration and a trend (P = 0.074) toward an increased 2:16α-OHE ratio. There were no significant increases in serum enterolactone concentrations in the treatment or placebo groups.
Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated.
ClinicalTrials.gov registration #NCT01089049.
herbal supplement; breast health; estrogen metabolites
Cell proliferation is associated with the pathogenesis of cancer because it provides opportunities for accumulating genetic mutations. However, biomarkers of cell proliferation in response to environmental stimuli have not been adequately explored for breast cancer risk.
In a case-control study of 200 breast cancer patients and 360 healthy controls, we investigated the association between phytohemagglutinin (PHA)-induced mitotic index in blood lymphocyte and breast cancer risk.
Having high mitotic index (>3.19%) was associated with an increased risk of breast cancer, with adjusted odds ratios (95% confidence interval) of 1.54 (1.03–2.30) and 2.03 (1.18–3.57) for all women and post-menopausal women, respectively. Mitotic index was correlated with some reproductive factors and body mass index in controls.
Our data suggest increased PHA-induced mitotic index in blood lymphocytes is associated with an increased breast cancer risk and that this association may be modulated by reproductive and other hormones.
breast cancer; mitogens; mitotic index; biomarker; cell proliferation; lymphocytes
The favorable prognosis for early stage breast cancer survivors may be a reason for the minimal research regarding their quality of life. Prior research has observed more long-term weight gain among early stage survivors compared to cancer-free women of a similar age. It would be useful to study survivors’ perceptions and reported behaviors regarding diet and exercise to see if there is a correlation with previous studies.
A sample of 700 breast cancer survivors from Ohio and Michigan was randomly selected from the Northwest Ohio affiliate of the Susan G. Komen For the Cure mailing list and sent a survey for completion.
389 survivors completed the survey and among Stage 1 (50/197 = 25.4%) and Stage 2 survivors (24/105 = 22.9%), a small proportion had a positive correlation between self-reported dietary behaviors and their perceived benefits of eating fruits and vegetables. Similar correlations were observed between their self-reported exercise behaviors and their perceived benefits of exercise (Stage 1: 36/197 = 18.3%, Stage 2: 18/105 = 17.1%).
Regardless of stage, a small proportion of survivors’ self-reported dietary and exercise behaviors match their perceived benefits of diet and exercise. Factors such as access, motivation, and lack of co-morbidities among early stage survivors may prevent them from living healthier post-diagnosis. More thorough dietary and clinical measurements will provide greater certainty. Thus, innovative, sustainable programs must be accessible and provide motivation and social support from family, friends, and other survivors to truly improve quality of life.
breast cancer; diet; exercise; activity
We investigated the relationship between mammary gland volume (MGV) of the breast as measured with three-dimensional chest computed tomography (CT) and breast cancer risk. Univariate analysis was used to assess the relationship between MGV and known risk factors in 427 healthy women. A case control study (97 cases and 194 controls) was conducted to assess breast cancer risk. MGV was significantly smaller for postmenopausal women than for premenopausal women, and was significantly larger for women with a family history of breast cancer than for women without. MGV, body mass index (BMI), and rate of family history of breast cancer were significantly higher among breast cancer patients than among healthy women, and number of deliveries was significantly lower among breast cancer patients. In postmenopausal women, age at menarche was significantly younger for breast cancer patients. MGV correlated well with breast cancer risk factors. The highest odds ratio was 4.9 for premenopausal women with the largest MGV. Regardless of menopausal status, the greater the MGV, the higher the odds ratio. Our results constitute the first reliable data on the relationship between MGV and breast cancer obtained through exact volume analysis.
mammographic density; mammary gland volume; breast cancer risk factor; breast cancer risk
The expression of basal cytokeratin markers CK5/6 in breast carcinomas has been associated with high histological grade and poor clinical outcome. A previous study has shown that CK5/6 can be detected in up to 17% of invasive lobular carcinomas (ILC). Here we study the expression of three basal cytokeratin markers (CK5/6, CK14, and CK17) in 53 ILC cases diagnosed by histology and lack of E-cadherin expression. Among them, 42 were classic lobular carcinomas, 6 were tubular-lobular carcinoma, and 5 were pleomorphic lobular carcinomas. There was no significant difference among these three groups in patients’ age, tumor size, uni- and multi-focality, expression of ER and PR, lymphovascular invasion, perineural invasion and lymph node metastasis. The only statistically different factor was HER2 over-expression, which was observed only in pleomorphic ILC (P = 0.0073). None of the 53 cases expressed CK5/6, CK14 or CK17; and 51/53 cases expressed luminal markers CK8 and CK18, and the two negative cases were both classic lobular carcinoma, with positivity for ER and PR. In conclusion, all 53 cases of ILC failed to show expression by any of the three basal CK markers, suggesting that very few ILC will demonstrate a basal phenotype when assessed by immunohistochemistry (IHC). More studies are needed to investigate molecular classification in lobular carcinoma of the breast.
lobular carcinoma of the breast; CK5; CK14 and CK17