bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-13-03: Hormone replacement therapy, is there an increased risk of in situ breast cancer ? data from a french cohort
Authors: Coussy F , Giacchetti S , Hamy A-S , Porcher R , Cuvier C , Lalloum M , de Roquancourt A , Albiter M , Espié M 
Published: August 2014

Abstract
Background: Use of hormone replacement therapy (HRT) has been associated with an increased risk of breast cancer. Few studies focus on correlation between HRT and in situ breast cancer A large cohort study, the Million Women Study (Reeves GK et al. Lancet Oncol. 2006) have shown that the use of HRT has been associated with an increased incidence of in situ breast cancer (RR = 1, 55, IC=1, 4–1,72, p = 0,03).
Purpose: We investigated the association between HRT use and duration and in situ breast cancer incidence from a data base of infraclinic breast lesions.
Materials & Methods: From 2007 to 2011, 2708 patients (pts) with a non palpable breast lesion were referred to our breast disease unit for exploration (Saint Louis Hospital, Paris). Radiological abnormalities were screened by mammography and/or breast ultrasound, and/or MRI. Out of 2708 pts, 1668 had a biopsy. All biopsies were seen by an anatomopathologist dedicated to breast. Here, we focus on the 1017 postmenopausal women (61%).
Results: Biopsies revaled invasive breast cancers in 222 pts (22%), in situ breast cancers in 164 pts (16%) [10 lobular in situ carcinoma and 154 ductal in situ carcinoma], high risk breast lesions in 103 pts (10%) and benign breast lesions in 528 patients (52%). Characteristics of the 164 patients with in situ breast cancer: median age 62 [IQR: 57 to 68], at least one pregnancy (mean number of pregnancies per woman, 1.6) 75,6%, family history of breast cancer:30,2%. Among these 164 patients, 42.6 % had used an oral contraceptive and 53% of them a HRT, with a mean duration of use of 7 years.
The HRT use was not significantly associated with in situ breast cancer (p = 0.66) as well as the duration of HRT.

Discussion: In this study of postmenopausal women, HRT use, whatever is the duration, was not associated with in situ breast cancer. Although a lack of statistical power may be invoked to explain these results, these findings suggest that the type of the HRT could be important to explain the difference between our study and the Million Women Study. In our study, the HRT used is in the majority of the pts, percutaneous oestrogens and natural progesterone as it is the most commun HRT used in France (Fournier A, Int J Cancer. 2005) during this period of time. Use and type of HRT are different in USA where conjugated estrogens and medroxy progestogerone acetate were commonly used.
Conclusion: We therefore encourage further studies to better appreciate the links between type of HRTs and in situ breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-03.
Abstract P4-13-09: The effect of weight change on breast adipose and dense tissue
Authors: Graffy HJ , Harvie MN , Warren RM , Boggis CR , Astley SM , Evans GD , Adams JE , Howell A 
Published: August 2014

Abstract
Background Observational studies indicate that weight gain or loss alters breast cancer risk. Hormonal prevention with tamoxifen or ovarian suppression reduces mammographic breast density, but has no impact on breast adipose tissue.1 The aim of this study was to assess whether change in weight is associated with change in breast density, breast fat or both.
Methods 74 premenopausal women aged between 35 and 45 years, with a family history of breast cancer, were recruited from our Family History Clinic. 36 were allocated to a 25% calorie-restricted Mediterranean diet and exercise intervention; a further 38 women were separately recruited into a control group and given written diet and exercise advice only. At baseline and 12 months breast dense and non-dense (largely adipose) components of the breast were measured: area using Cumulus2 and volume using the Manchester ‘stepwedge’ method.3 Visual assessment of percentage density was reported to the nearest 5%.4 We used correlations to relate percentage change in absolute dense and non-dense (area and volume) to percentage change in: weight, total body fat (DXA), intra-abdominal and subcutaneous abdominal fat (MRI), as well as serum total IGF-I.
Results At 12 months, 40 (54%) women lost &gt;1.5% body weight, 14 (19%) gained &gt;1.5% and 21 (28%) remained weight stable, &lt;+/−1.5% weight change. There was a range of percentage weight change from −16.3% to +9.8%. There were no significant changes in dense area (r = −0.14 p = 0.29) or volume (r = −0.01 p = 0.97) with weight change. However, both the area and volume of non-dense breast tissue changed significantly in relation to change in body weight (r = 0.52 p &lt; 0.0001 & r = 0.78 p &lt; 0.0001 respectively), total body fat (r = 0.49 p &lt; 0.001 & r = 0.75 p = &lt;0.0001 respectively), intra-abdominal fat (r = 0.45 p &lt; 0.0001 & r = 0.36 p = 0.03 respectively) and subcutaneous abdominal fat (r = 0.55 p &lt; 0.0001 & r = 0.52 p = 0.002 respectively). Visually assessed percentage mammographic density was significantly inversely related to weight (r = −0.27 p = 0.038). Serum total IGF-I was not significantly correlated with breast dense area. (r = −0.21 and p = 0.09).
Conclusions These data indicate that dense area and volume remain stable irrespective of change in weight. Non-dense area changes significantly in response to weight change in parallel with total and abdominal fat stores. These observations were performed on relatively small numbers of women and require confirmation in larger series.
1. Cuzick et al J Natl Cancer Inst. 103(9): 744–52, 2011. 2. Boyd NF et al J Natl Cancer Inst. 87(9) 670–675 1995. 3. Diffy et al IWIDM 2006, LNCS 4046 p1-9. In Astley et al (Eds) Springer-Verlag Berlin Heidelberg 2006 4. Brisson J et al. Cancer Epidemiol Biomarkers Prev 2003;12:7288–32.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-09.
Abstract P4-13-10: Do BRCA1 and BRCA2 mutation carriers have an earlier natural menopause than their non-carrier relatives: A study from the Kathleen Cuningham Foundation Consortium For Research Into Familial Breast Cancer (kConFab).
Authors: Collins IM , Milne RL , McLachlan SA , Friedlander M , Birch KE , Weideman PC , Hopper JL , Phillips K-A 
Published: August 2014

Abstract
BACKGROUND: Limited data from the in vitro fertilisation setting suggest that germline BRCA1 mutations are associated with occult primary ovarian insufficiency. We examined whether carriers of a BRCA1 or BRCA2 mutation have earlier natural menopause than their non-carrier relatives.
PATIENTS AND METHODS: Eligible subjects were female mutation carriers and tested non-carriers from families segregating BRCA1 or BRCA2 mutations enrolled in KConFab. Women who had not been tested for the family mutation and those with primary amenorrhoea were excluded. Data were self-reported using uniform questionnaires completed at cohort entry and every 3 years thereafter. Age at natural menopause (NM) was defined as age at cessation of menses for ≥ 12 months in the absence of other causes. Cox proportional hazards analysis was applied, modelling time in years from birth to NM, adjusting for year of birth (continuous), body mass index (continuous), ever regular cigarette smoking (no, yes), and ever regular alcohol use (no, yes). Analysis time was censored at the earliest of: cessation of menses for 12 months in the absence of other reasons (natural menopause), last follow-up, pelvic surgery including oophorectomy or hysterectomy, commencement of hormone replacement therapy or Tamoxifen as a risk reducing medication, or any cancer diagnosis. Hazard ratios (HR) were estimated as a measure of how rapidly mutation carriers reach natural menopause relative to non-carriers.
RESULTS: No difference was observed in the rate at which carriers and non-carriers went through natural menopause, regardless of the gene mutated in the families. The adjusted hazard ratio estimates were 0.97, (95% CI 0.69–1.35, p = 0.8) for BRCA1 mutation carriers versus non-carriers and 1.02, (95%CI 0.72–1.44, p = 0.9) for BRCA2 mutation carriers versus non-carriers.

CONCLUSIONS: This study found no evidence that BRCA1 and BRCA2 mutation carriers do reach natural menopause at an earlier age than their non-carrier relatives.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-10.
Abstract P4-14-09: Feasibility of liposuction for treatment of arm lymphedema from breast cancer.
Authors: Doren EL , Smith PD , Sun W , Lacevic M , Fulp W , Reid R , Laronga C 
Published: August 2014

Abstract
Background: Lymphedema is a dreaded complication of breast cancer treatment affecting 20% of women having axillary node dissection. Liposuction minimizes unwanted fat in targeted areas. Our objective was to explore the feasibility of liposuction to reduce fat volume and thus arm lymphedema.
Methods: An IRB-approved prospective trial was conducted of women having unilateral arm lymphedema resulting from breast cancer treatment. At enrollment there was no evidence of cancer recurrence or arm cellulitis. Arm measurements (circumferential), volumes (water displacement and geometric calculation), and muscle strength differences between the affected and unaffected arms and quality of life/functionality were measured pre-operatively and post-operatively at 6 weeks, 6 months and one year(s). Descriptive statistical analysis was performed.
Results: Six breast cancer survivors underwent the liposuction procedure from 12/2008–4/2011. Median age was 54 yrs (range: 43–60) and median volume of fat aspirated was 700mls (range: 350–700). Average volume difference between the affected and unaffected arms at baseline was 522.5 mls (176–867) (geometric) and 589.2mls (280–770) (water displacement). No immediate complications; 1 cellulitis at 4 months post-operative. Average percent volume reductions for 5 of the 6 women at 6 weeks, 6 months and 1 year were 70%, 47%, 71% mls geometrically and 63%, 18%, 54% by water displacement respectively. Quality of life and functionality improved in all patients. Muscle strength remained unchanged. Pain lessened. Average follow-up is 15.49 months (range: 1.8–24.84 months).
Conclusion: Liposuction can safely reduce volume of arm lymphedema and improve functionality/quality of life. Larger studies (longer follow-up) are required to validate the durability of these early results.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-09.
Abstract P4-14-13: Therapeutic mammaplasty does not cause a delay in the delivery of chemotherapy in high risk breast cancer patients
Authors: Khan J , Barrett S , Stallard S , Forte C , Weiler-Mithoff E , Reid I , Winter A , Doughty J , Romics L 
Published: August 2014

Abstract
Introduction: oncosurgical safety of therapeutic mammaplasty (TM) is widely investigated. The interval between surgery and delivery of adjuvant chemotherapy is an integral part of overall oncological safety. Therefore, we examined the time between TM and AC, and compared it to wide local excision (WLE) and mastectomy (Mx) with or without immediate breast reconstruction (IBR), respectively.
Methods: data of 174 patients who underwent TM, WLE and Mx±IBR was analyzed retrospectively. All patients were operated within three breast units of Glasgow during a period of 48 months. Time between decision to offer adjuvant chemotherpay and delivery of the first cycle of chemotherapy was analyzed. Significance was calculated with Mann-Whitney and Kruskal-Wallis tests (two and four groups compared, respectively).
Results: median time to adjuvant chemotherapy after TM (n = 36) was 29 [16–58] days, WLE (n = 66) was 29.5 [15–105], Mx only (n = 56) was 29 [15–57], and Mx and IBR (n = 16) was 31 [15–58] days. No significant difference was found in terms of time to adjuvant chemotherpay in patients treated with TM compared to WLE (p = 0.384), Mx only (p = 0.828) or Mx and IBR (p = 0.366). Further, there was no significant difference when a cumulative comparison of the four groups was carried out (p = 0.507).
Conclusions: our data indicate that oncosurgical safety of TM in terms of time to chemotherapy is similar to other high risk breast cancer patients treated WLE and Mx with or without IBR. This also suggests that there is no significant difference in postoperative complication rates after these four ways of surgical treatment of breast cancer, which would possibly be the primary cause for a delay in delivering adjuvant chemotherapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-13.
Abstract P4-15-03: Patterns of relapse following re-irradiation of the breast using partial breast brachytherapy (PBB)
Authors: Chadha M , Boachie-Adjei K , Boolbol SK , Kirstein L , Osborne MP , Tarter P , Harrison LB 
Published: August 2014

Abstract
Purpose: This study is undertaken to evaluate the patterns of relapse among patients with a prior history of irradiation where the RT field included the breast, and who received re-irradiation using PBB for a localized second cancer event in the breast using partial breast.
Materials and Methods: Twenty-seven patients were enrolled in an IRB approved study. Nineteen patients had prior history of breast cancer treated with lumpectomy and external beam therapy (ERT), and 8 patients had prior history of mantle RT. All patients underwent lumpectomy with negative margins and received a median dose of 45Gy PBB. The median time interval between the primary breast cancer diagnosis and the second cancer event in the ipsilateral breast is 94-months (range 28-months to 211-months). The median time between mantle RT and the breast cancer is 245 months.
Results: At a median follow up of 73 months following lumpectomy and PBB 14.8 % (4/27) patients developed a local recurrence and were salvaged by mastectomy. The 5-year Kaplan Meier local disease-free survival and mastectomy-free survival is 100% and 81%, respectively. Remarkably, one third of patients with prior history of mantle RT developed third primary cancers (pancreas, lung and renal). All patients with the third primary cancers died free of any relapse from the breast cancer. None of the patients with prior history of breast cancer developed a second malignancy, and 3/21 developed distant metastases.
Conclusions: In appropriately selected patients with prior history of lumpectomy and ERT for breast cancer we observed a high rate of local control and freedom from mastectomy. Patterns of relapse among patients with prior mantle RT suggest that breast conservation and PBB was appropriate for treating early stage disease. Breast conservation therapy did not have a detrimental effect on breast cancer specific outcome and eventual patient survival. Patients motivated for breast conservation may have an alternative to mastectomy at initial diagnosis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-15-03.
Abstract P5-01-11: ‘Same-day diagnosis’ of women suspected of breast cancer: success rate and impact on diagnostic quality and patients' anxiety levels
Authors: Barentsz MW , Wessels H , van Diest PJ , Pijnappel RM , van der Pol CC , Witkamp AJ , van den Bosch MA , Verkooijen HM 
Published: August 2014

Abstract
Introduction: Uncertainty about a breast cancer diagnosis is a stressful event. As such, many initiatives have been undertaken to reduce the time of uncertainty by providing ‘same-day diagnosis’ for patients suspected of breast cancer. However, only few studies have evaluated the feasibility of ‘same-day diagnosis’ diagnosis, while the impact of ‘same-day diagnosis’ on diagnostic accuracy and patient anxiety has hardly been studied at all. This study aims to evaluates feasibility, diagnostic accuracy and impact on patients' anxiety of ‘same-day diagnosis’ of patients suspected of breast cancer.
Materials and Methods: In November 2011, the ‘same-day diagnosis’ system was implemented in our hospital. This system consists of completing the following items on the day of the first visit: 1. Clinical examination, imaging (mammography, ultrasound), and (if necessary) FNA or core needle biopsy2. High speed processing of biopsy specimens using Leica Peloris tissue processor3. Multidisciplinary evaluation of clinical, imaging and histological findings4. Communication of the final diagnosis and treatment plan to the patient
All patients presenting for ‘same-day diagnosis’ are entered prospectively in a database. Feasibility of ‘same-day diagnosis’ is evaluated, and reasons for failure are scrutinized. Diagnostic quality of ‘same-day diagnosis’ is evaluated by linking all patients to PALGA (Dutch National Pathology Database) six months following the day of diagnosis, in order to identify false negative results (i.e. missed cancers) and false positive results (i.e. ‘cancers’ turned out to be benign during further work-up). Impact of ‘same-day diagnosis’ on patient anxiety is measured by the 4-item State Trait Anxiety Inventory, which is filled out by patients on several occasions on the day of diagnosis as well as during the first seven days following diagnosis.
Results: Between November 2011 and May 2012, 266 women were eligible for ‘same-day diagnosis’. Fifty-eight patients (22%) were diagnosed with breast cancer. Overall, 80% of the patients received a final diagnosis within one day. For patients with cancer, this proportion was somewhat lower, i.e. 71%. Accuracy of ‘same-day diagnosis’ and impact on patients' anxiety are currently under study.
Conclusion: ‘Same-day diagnosis’ is feasible for the far majority of patients suspected of breast cancer. Evaluation of implementation of ‘same-day diagnosis’ on diagnostic quality and impact on patient anxiety is crucial. Updated results will be presented in December 2012.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-11.
Abstract P5-03-04: Effect of aging on the function and transformation of murine mammary stem cells
Authors: Bandyopadhyay A , Dong Q , Wang D , Gao H , Wu A , Yeh I-T , Sun L 
Published: August 2014

Abstract
Epidemiological studies have shown that the risk of getting breast cancer progressively increases with age. A woman is 100 times more susceptible to develop breast cancer in her 60s than in her 20s. A better understanding of altered cellular and molecular mechanisms leading to the development of sporadic breast cancers as a result of aging are urgently needed for its prevention and treatment in growing population of older women. Recent research implicated that adult mammary stem cells (MaSCs) might be responsible for the initiation and progression of certain types of breast cancer. But no studies have been reported on how lifelong exposure of MaSCs to endogenous and environmental stresses during aging compromises their self-renewal and differentiation function and predispose them to neoplastic transformation either spontaneously or after carcinogen exposure. In our study, we have investigated the effect of progressive aging and carcinogen exposure on MaSC number and function in a murine model. The FACS isolated MaSC enriched basal cells, characterized by their immunophenotype (Lin−CD49fhighCD24med) were utilized to evaluate MaSC frequency and function during aging by in vitro mammosphere formation and 3D-ECM sphere differentiation assay as well as by in vivo cleared mammary fat pad transplantation (IVT). The results of our study showed that the percentage of MaSCs analyzed by both FACS profile and in vitro assays, increased steadily with increasing age observed at 2, 7, 17 and 25 month-old C57BL/6 mice. Subsequent IVT using mammosphers or 3D structures formed by young (4 months) and old MaSCs (28 months) derived from C57BL/6 mice showed similar in vivo functional mammary gland regenerative capacity indicating similar self-renewal/differentiation ability between young and old MaSCs. However, we found that the regenerated glands from old MaSCs had significantly higher number of spontaneous pre-neoplastic lesions (52.0%) than those from young MaSCs (18.3%). Significantly, MaSC frequency was also increased by the in vivo exposure of a carcinogen, N-Methyl-N-Nitrosourea (MNU, 25 mg/kg body weight, once a week for three consecutive weeks), in old mice with no effect on total mammary cell number. Furthermore, the old MaSCs expanded by MNU treatment were still capable of in vivo regeneration with similar success rate as that of normal old MaSCs. But, we observed increased frequency of hyperplasia and dysplasia in the regenerated glands initiated by MNU treated old MaSC. Our results indicate that MaSCs might be the precursors of preneoplastic lesions and old MaSCs appear to be predisposed to premalignant transformation, which is enhanced by the exposure to a DNA damaging agent.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-04.
Abstract P5-03-05: Histone deacetylase (HDAC)-inhibitor mediated reprogramming drives cancer cells to the pentose phosphate metabolic pathway
Authors: Debeb BG , Larson RA , Lacerda L , Xu W , Smith DL , Ueno NT , Reuben JM , Gilcrease M , Krishnamurthy S , Buchholz TA , Woodward WA 
Published: August 2014

Abstract
Recent studies have shown that energy metabolism in human pluripotent cells contrasts sharply with energy metabolism in differentiated cell types. Specifically, it has been shown that nuclear reprogramming from somatic cells to induced pluripotent stem cells is associated with a switch from oxidative to glycolytic metabolism. Whether a metabolic switch also occurs in reprogrammed/dedifferentiated breast cancer cells is unknown. Moreover, the function of the metabolic state in stemness is poorly understood and no data are available on whether breast cancer stem cells (CSCs) are metabolically different from committed cancer cells. Herein we demonstrated that HDAC inhibitors reprogram committed single aldefluor negative breast cancer cells into aldefluor positive cells (10.3 ± 2.8 vs 21.3 ±3.7% untreated vs treated P &lt;0.05, representing an average of 5 single cell derived clones) and promoted tumor initiation from non-initiating committed cells (p = 0.004). Further, induced stem-like cells were resistant to taxol and salinomycin, a drug previously described to target CSCs. These reprogrammed cancer cells have enhanced activity of the pentose phosphate pathway (PPP) with upregulation of G6PD expression and activity and higher levels of NADPH and ROS. Hypothesizing that CSCs may favor the PPP in order to survive and self renew, we used G6PD inhibitors, 6-AN and Imatinib, to target mammosphere formation and aldefluor activity in HDAC inhibition induced stem-like cells. Not only was there a significant decrease in mammospheres from reprogrammed cells, the aldefluor activity was totally blocked at a concentration that does not affect proliferation. This work demonstrates that HDAC inhibition mediated cancer cell dedifferentiation promotes metabolic reprogramming and highlights an FDA approved drug that targets metabolism in stem cell plasticity. Further functional endpoint studies are underway to validate these findings.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-05.