Initial Breast Cancer Diagnosis Research Articles

Incidence, risk factors and survival of patients with brain metastases at initial metastatic breast cancer diagnosis in China

PurposeTo characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. MethodsThe China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. ResultsBrain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40–4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02–3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52–6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment. ConclusionHER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.

Widespread Metastasis to the Stomach 10 Years After Primary Breast Cancer: A case report and review of the literature.

Rationale:Breast cancer is a common malignant tumor. The most common metastatic sites of breast cancer are the bone, brain, liver and lung, and gastrointestinal metastases are rare. Considering that the median time interval from the initial breast cancer diagnosis to stomach metastasis is 77.5 months, gastrointestinal metastases are rarely observed 10 years after primary breast cancer.Patient concerns:Here, we present a 63-year-old female with unusual endoscopy results that revealed scattered polyps and mucosal infiltration throughout the stomach, which were later confirmed to be metastatic lobular carcinoma of the breast that had been surgically removed 10 years earlier.Diagnosis:The patient was diagnosed with gastric metastases of breast cancer by immunohistochemistry.Interventions:The patient underwent endocrine therapy with palbociclib and tamoxifen.Outcomes:After 1 year of endocrine therapy, the symptoms of upper abdominal discomfort and fatigue were relieved and a new gastroscopy revealed there had been no significant progression of the gastric metastasis. According to the Response Evaluation Criteria in Solid Tumors (RECIST), the patient reached a state of stable disease.Lessons:Gastric metastases of breast cancer are rare in the clinical setting. However, considering the possibility of gastric metastases from breast cancer and performing an upper endoscopy are crucial for patients who present with any subtle gastric symptoms and have a past medical history of breast cancer, even if the breast cancer occurred more than 10 years ago.

Depression and sleep disorders are associated with early mortality in women with breast cancer in the United Kingdom

BackgroundThe aim of this study was to estimate the association between common mental disorders and mortality in breast cancer patients. MethodsThis retrospective cohort study included women aged 18–80 for whom an initial diagnosis of breast cancer was documented in one of 200 general practices in the UK between January 2008 and December 2012. The main outcome of this study was the mortality within 5 years of the index date as a function of depression, anxiety disorder, and sleep disorders, using Cox regression models. ResultsA total of 6656 women (mean age: 57.9 (standard deviation: 12.0 years)) were included in the study. Within 5 years of the index date, 461 (6.9%) of women were deceased. Depression (HR: 1.44 (95% CI: 1.17–1.78)), and sleep disorders (HR: 1.37 (95% CI: 1.02–1.84)) were significantly associated with death within 5 years. ConclusionsIt is important to treat BC patients with chronic diseases holistically and to take psychological comorbidities seriously as factors influencing the survival of patients in order to counteract the considerable mortality rate of BC patients.

Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from the real-world, observational BREAKOUT study

BackgroundThe global observational BREAKOUT study investigated germline BRCA mutation (gBRCAm) prevalence in a population of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC).MethodsEligible patients had initiated first-line cytotoxic chemotherapy for HER2-negative MBC within 90 days prior to enrollment. Hormone receptor (HR)-positive patients had experienced disease progression on or after prior endocrine therapy, or endocrine therapy was considered unsuitable. gBRCAm status was determined using baseline blood samples or prior germline test results. For patients with a negative gBRCAm test, archival tissue was tested for somatic BRCAm and homologous recombination repair mutations (HRRm). Details of first-line cytotoxic chemotherapy were also collected.ResultsBetween March 2017 and April 2018, 384 patients from 14 countries were screened and consented to study enrollment; 341 patients were included in the full analysis set (median [range] age at enrollment: 56 [25–89] years; 256 (75.3%) postmenopausal). Overall, 33 patients (9.7%) had a gBRCAm (16 [4.7%] in gBRCA1 only, 12 [3.5%] in gBRCA2 only, and 5 [1.5%] in both gBRCA1 and gBRCA2). gBRCAm prevalence was similar in HR-positive and HR-negative patients. gBRCAm prevalence was 9.0% in European patients and 10.6% in Asian patients and was higher in patients aged ≤ 50 years at initial breast cancer (BC) diagnosis (12.9%) than patients aged > 50 years (5.4%). In patients with any risk factor for having a gBRCAm (family history of BC and/or ovarian cancer, aged ≤ 50 years at initial BC diagnosis, or triple-negative BC), prevalence was 10.4%, versus 5.8% in patients without these risk factors. HRRm prevalence was 14.1% (n = 9/64) in patients with germline BRCA wildtype.ConclusionsPatient demographic and disease characteristics supported the association of a gBRCAm with younger age at initial BC diagnosis and family history of BC and/or ovarian cancer. gBRCAm prevalence in this cohort, not selected on the basis of risk factors for gBRCAm, was slightly higher than previous results suggested. gBRCAm prevalence among patients without a traditional risk factor for harboring a gBRCAm (5.8%) supports current guideline recommendations of routine gBRCAm testing in HER2-negative MBC, as these patients may benefit from poly(ADP-ribose) polymerase (PARP) inhibitor therapy.Trial registrationNCT03078036.

Yttrium-90 Glass Microsphere Transarterial Radioembolization for Patients with Unresectable Liver-Dominant Breast Cancer Metastasis

Transarterial radioembolization (TARE) using Yttrium-90 (Y90) microspheres is a potential therapeutic option for treatment-refractory, unresectable, liver-dominant breast cancer metastases (LdBM). We hypothesized that Y90 TARE is an effective and safe treatment for delaying progression in patients with LdBM. In this IRB approved (MCC 18294) study, we retrospectively analyzed institutional database to identify patients with unresectable and chemotherapy-refractory LdBM who underwent Y90 TARE. We extracted patient demographics, systemic therapy details and imaging studies for response assessment. Liver function tests, CA15-3 level, Albumin-Bilirubin (ALBI) and Model for end-stage liver disease (MELD) score were assessed at baseline, 1- and 3-months post TARE to evaluate for hepatotoxicity. Hepatic progression-free (hPFS) and overall survival (OS) were estimated using Kaplan-Meier analysis, and compared using log-rank test. Cox regression was performed to evaluate the effect of predictors on defined outcomes. Maximum toxicity grade was reported using Common Terminology Criteria for Adverse Events version 5. Between 2010-2019, 32 patients with LdBM underwent 51 TARE sessions with Y90 glass microsphere. All patients progressed through systemic therapy. Median age was 61 years (range 27-81). Interval to develop liver metastasis from initial breast cancer diagnosis was 5-years (median). Median follow-up duration after TARE was 11 months (range, 1-44). 18 patients had sequential bilobar treatment, 1 sequential segmental, 9 unilobar right, 1 unilobar left, 2 segmental and 1 whole-liver single session TARE. Median hPFS and OS after TARE were 7-months (95% CI 5.0–9.1) and 13 months (95% CI 9.2–16.8), respectively. The 6-months and 1-year actuarial hPFS were 52% and 21%; and 1-year and 2-year OS were 58.5%, and 35.7%, respectively. Factors independently predicting worse hPFS were age <60 years (6-month hPFS 41.3% vs 62.5%, p = 0.04) and bilobar disease (33.3% vs. 68.8%, p = 0.005). On multivariate analysis, bilobar disease (p = 0.01) and high baseline CA 15-3 (p = 0.05) were predictors of longer OS. No significant change was noted in ALBI, MELD, total bilirubin, albumin and alkaline phosphatase levels at 1- and 3-months post-TARE. Grade 3 toxicity was noted in 3-patients (9.4%), all received sequential bilobar treatment, necessitating hospitalization for pain (2-patients), and worsening liver function (1-patient). The 30-day mortality was 3.1%; 1 patient died from radioembolization-induced liver disease. For patients with therapy-refractory unresectable LdBM, Y90 TARE is effective and relatively safe. TARE can potentially delay progression allowing patients with LdBM to continue systemic therapy longer.

Second primary breast cancer after diagnosis of breast cancer among male patients: An examination of population characteristics and overall survival.

BackgroundMale patients with breast cancer (BrC) have increased risk of developing 2nd-primary BrC (2nd-BrC). Given the relative rarity of male BrC, population-based registries are needed to analyze overall survival (OS) outcomes for these patients.MethodsUsing the Surveillance, Epidemiology and End Results registry of patients diagnosed from 1975 to 2016, a cohort study of men whose only malignancy was BrC (BrC—O; n = 6,475), and men who developed 2nd-BrC after initial BrC diagnosis (BrC-2; n = 85) was performed. The standardized incidence ratio (SIR) of 2nd-BrC, Kaplan-Meier OS and multivariable Cox regression modelling were performed.FindingsThe SIR for 2nd-BrC was 32.95 (95%CI:[23.85–44.38],p < 0.05). The majority (88%) of 2nd-BrC for BrC-2 were contralateral from 1st-BrC; suggesting the unlikeliness of miscoding local recurrences as 2nd-BrC for most patients. There was no statistically significant difference between rates of hormone (reported in 44%) or HER-2 (reported in 33%) receptor status between BrC-O and BrC-2, albeit with limited data. The 2nd-BrC for BrC-2 was significantly more likely to be localized or distant stage (rather than regional) than BrC-O. Median OS was 103 months (95% CI: [99, 108]) for BrC-O and 62 months (95% CI [49, 128] after 2nd-BrC. When sub-grouped by BrC stage, and when analyzed by Cox regression, there was no significant difference in OS between BrC-O and BrC-2.InterpretationPatients with male BrC are at significantly increased risk of 2nd BrC, but they can expect similar post-BrC prognosis (versus those without 2nd-BrC), after adjusting for patient demographics and tumor characteristics known to affect OS.FundingNone.

Association of patient factors with time to treatment for breast cancer.

Studies have shown that in the United States, there is an increasing time from breast cancer diagnosis to first treatment (time to treatment or "TTT"), with concern that such delays may worsen oncologic outcomes. A component of TTT is the time from the initial diagnosis to initial surgical consultation (SC). We sought to identify patient-related factors associated with time to initial SC, and evaluate how this interval is associated with overall total time to treatment (TTT). A prospective database of women diagnosed with breast cancer at our institution from 2015 to 2016 was reviewed. Time from initial breast cancer diagnosis to SC and overall TTT was collected from the electronic medical record. Documented patient-identified preferences regarding scheduling the first surgical appointment were reviewed. A multivariate analysis was performed to determine clinical and patient factors associated with TTT. Of 553 breast cancer patients included in the study, 27% of women opted for the earliest appointment while 73% chose a later date. The median time from diagnosis to SC was 8.5±4.7days. Patients who accepted a first available SC waited an average of 5.6±3.4days, while those who deferred waited 9.5±4.6days (P<.001). Patients who deferred the earliest available SC were older, with a median age of 67 versus 63years, (P=.018), and had a preference for a specific location in the geographical hospital region (P=.003). Patients who deferred the first available SC also had a longer TTT (33 vs. 28days, P=.027). Among newly diagnosed breast cancer patients, there is a substantial population that defers the first available SC. These patients are also more likely to have a prolonged TTT. Future follow-up of this cohort is necessary to determine the delays on TTT affect cancer outcomes and overall survival.

Impact of Healthcare Access Disparities on Initial Diagnosis of Breast Cancer in the Emergency Department.

Breast cancer continues to be the second leading cause of cancer deaths in women in the United States. This is more noticeable in communities with pronounced healthcare disparities. The aim of this study was to investigate the different demographics that might play a role in the detection of breast cancer in a county hospital emergency department (ED).A retrospective study was conducted of female patients diagnosed with breast cancer over a five-year period (1/1/2015 to 12/31/2018). Patients with breast cancer as the primary or secondary diagnosis were identified.This study shows that 66 (73.3%) women diagnosed in the ED were Hispanic or African American. There was a significant delay (a median of 461 days) in the time between the diagnosis of suspected breast cancer in the ED to their follow-up visit with definitive diagnosis in a primary care clinic.These findings suggest that women with a suspected breast cancer diagnosis who are seen in a safety net hospital and have Medicaid funding may have significant delays before final diagnosis is made. Patient demographics could have an impact on the patients' access to screening and regular healthcare visits, hindering an early breast cancer diagnosis by a primary care provider.

Pre-operative axillary ultrasound with fine-needle aspiration cytology performance and predictive factors of false negatives in axillary lymph node involvement in early breast cancer

Breast cancer is the most common cancer among females worldwide. Axillary lymph node involvement is an important prognostic factor in pre-operative evaluation. The aim of this study was to evaluate the sensitivity and accuracy of AUS during the initial breast cancer diagnosis and the contribution of ultrasound with guided FNAC (AUS + FNAC) in cases of suspicious node. A retrospective study was conducted at the Lorraine Cancer Institute between 1 January and 31 December 2015. It included patients with early breast cancer, all of whom received AUS. If axillary node involvement was suspected, FNAC was performed. Sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) were performed depending on FNAC results. In total, 292 patients were included. 88 patients (30.1%) had a suspicious lymph node on ultrasound and had FNAC, of whom 53 tested positive for axillary node involvement (60.2%). Among the 35 patients who tested negative with FNAC, 15 had axillary metastatic involvement. Performance of AUS + FNAC was better than that of AUS alone, with sensitivity, specificity, positive predictive and negative predictive values of approximately 44.5%, 100%, 100% and 72.4%, respectively, and accuracy of approximately 77.4%. Luminal A subgroup, axillary involvement of less than two positive nodes or nodal tumor of less than 7mm are independent factors of false negative rate. AUS performance would seem to be improved by FNAC, with a false negative rate of approximately 26%. It may be possible to reduce the false negative rate of AUS if its contributing factors are taken into consideration, along with the impact of specific echographic signs as revealed by experienced radiologists.

A Comparison Between the Online Prediction Models CancerMath and PREDICT as Prognostic Tools in Thai Breast Cancer Patients.

Background and PurposeWeb-based prognostic calculators have been developed to inform about the use of adjuvant systemic treatments in breast cancer. CancerMath and PREDICT are two examples of web-based prognostic tools that predict patient survival up to 15 years after an initial diagnosis of breast cancer. The aim of this study is to validate the use of CancerMath and PREDICT as prognostic tools in Thai breast cancer patients.Patients and MethodsA total of 615 patients who underwent surgical treatment for stage I to III breast cancer from 2003 to 2011 at the Division of Head Neck and Breast Surgery, Department of Surgery, Siriraj Hospital, Mahidol University, Thailand were recruited. A model-predicted overall survival rate (OS) and the actual OS of the patients were compared. The efficacy of the model was evaluated using receiver-operating characteristic (ROC) analysis.ResultsFor CancerMath, the predicted 5-year OS was 88.9% and the predicted 10-year OS was 78.3% (p<0.001). For PREDICT, the predicted 5-year OS was 83.1% and the predicted 10-year OS was 72.0% (p<0.001). The actual observed 5-year OS was 90.8% and the observed 10-year OS was 82.6% (p<0.001). CancerMath demonstrated better predictive performance than PREDICT in all subgroups for both 5- and 10-year OS. In addition, there was a marked difference between CancerMath and observed survival rates in patients who were older as well as patients who were stage N3. The area under the ROC curve for 5-year OS in CancerMath and 10-year OS was 0.74 (95% CI; 0.65–0.82) and 0.75 (95% CI; 0.68–0.82). In the PREDICT group, the area under the ROC curve for 5-year OS was 0.78 (95% CI; 0.71–0.85) and for 10-year OS, it was 0.78 (95% CI; 0.71–0.84).ConclusionCancerMath and PREDICT models both underestimated the OS in Thai breast cancer patients. Thus, a novel prognostic model for Thai breast cancer patients is required.

An investigation of the fertility needs of young patients with breast cancer

Objective: To investigate the fertility needs and outcome of pregnancy in patients with young breast cancer in China. Methods: A retrospective cross-sectional investigation was conducted on 374 young breast cancer women from Cancer Hospital, Chinese Academy of Medical Sciences. Young patients with breast cancer were defined as patients who got initial diagnosis of breast cancer at age no more than 40 years old. We conducted a questionnaire survey and collected clinical data from medical chart. Logistic regression model was used to analyze the possible factors influencing patients' fertility intention. Results: 308 young women with breast cancer completed questionnaires, and the response rate was 82.4%. 81 patients (26.3%) had fertility needs after diagnosis. Of them, 6 cases took active measures to preserve fertility. 72 patients (23.4%) received fertility counseling during treatment. 7 patients were successfully pregnant, including four cases who delivered normally. Multivariate logistic regression analysis showed that patients under 35 years old (OR=4.81), bachelor degree or above (OR=3.26), receiving breast-conserving surgery (OR=2.15) and childless patients (OR=3.03) were more likely to have fertility needs after diagnosis of breast cancer (all P<0.05). Conclusions: The fertility needs of young breast cancer women in China are gradually increasing. Healthcare providers associated with tumor patients should actively offer corresponding fertility consultation and individualized diagnosis and therapy plans for patients with fertility needs.

Effect of ARID1a oncogenic loss of function mutations on overall survival in metastatic breast cancer patients.

e13068 Background: ARID1a (AT Rich Interactive Domain 1A) is part of the SWI/SNF complex, which regulates gene transcription. Its inactivation has been shown to determine resistance to endocrine therapy via enrichment of basal-like gene expression features [Xu G., 2020]. We recently reported that ARID1a lower gene expression might be associated with worse overall survival (OS) [Mariotti V., 2019]. The aim of this study was to analyze the effect of ARID1a mutations on survival in metastatic breast cancer patients (pts). Methods: Breast cancer patients prospectively consented for inclusion in the ORIEN genomic database with known metastatic disease were analyzed using cBioPortal. Predicted biologic effect of mutations from RNASeq data was determined by OncoKB. OS was calculated from initial breast cancer diagnosis to death from any cause. OS analysis using Kaplan Meier and descriptive statistics were performed on SPSS. Results: We identified 644 pts with metastatic breast cancer. Of these, 88 (12.8%) pts harbored an ARID1a mutation. 62 (70.5%) mutations were missense (biologic effect unknown), the remaining 26 (29.5%) were oncogenic loss of function (OLF) changes (frame-shift, deletion, insertion, or nonsense). Median OS was significantly better in patients harboring missense mutations compared to OLF and wild type mutations [median OS 58.2 months (95% CI 44.5-71.8) with missense mutations vs 22.8 months (95% CI 10.8-34.7) with OLF mutations and 27.48 months (95% CI 24.5-30.3) with wild type]. Demographics, tumor features and chemotherapy use were generally equally distributed among the subgroups (table). Conclusions: In our study the median OS was worse in metastatic breast cancer pts harboring OFL ARID1a mutations compared to pts with wild type ARID1a or harboring missense ARID1a mutations. Further studies are warranted to assess how specific ARID1a mutations might affect survival in metastatic breast cancer pts. [Table: see text]

Association between thyroid gland diseases and breast cancer: a case-control study.

At the present time, there is no consensus on the association between benign thyroid diseases and breast cancer (BC). Therefore, the aim of this study is to help shed some light on the association between hyperthyroidism, hypothyroidism, and thyroiditis and breast cancer risk. Use of the Disease Analyzer database (IQVIA) enabled us to perform a retrospective case-control study of 7408 women aged between 18 and 80, who were treated for an initial breast cancer diagnosis in a general practice in the United Kingdom between 2006 and 2015 (index date). Patients with a previous cancer diagnosis and an observation time of less than 12months prior to the index date were excluded. The control group consisted of 7408 healthy women, who were matched to cases 1:1 by age, body mass index, hormone replacement therapy, and physician. The main outcome parameters of this study were the presence of thyroid disease (hypothyroidism, hyperthyroidism, struma, and thyroiditis) and the TSH values in the two groups. A univariate logistic regression model was used to investigate the association between benign thyroid diseases, TSH values, and BC. The mean age was 58.4years in both groups. We found a significant association between thyroiditis and BC (OR: 1.91, p = 0.01) and were able to refute the association between hyperthyroidism/hypothyroidism and BC. We also found that thyroid-stimulating hormone (TSH) had no significant effect on breast cancer risk. Many experimental studies suggest a link between hyperthyroidism/hypothyroidism and BC. We were able to demonstrate an epidemiological association between thyroiditis and an increased BC risk. This shows the need for close monitoring for BC in women with thyroiditis.

SUN-927 Ectopic Cushing Syndrome Due to a Metastatic Neuroendocrine Tumor to the Breast

Introduction:We present a rare case of ectopic Cushing syndrome (CS) due to a neuroendocrine tumor (NET) metastatic to the breast.Case:A 38-year-old female was referred for ACTH-dependent CS. She had rapid development of cushingoid features and hypertension three months prior to presentation. A 24-hour urinary free cortisol (UFC) was elevated to 2548 μg (0-50 μg/24hr), and ACTH was 228 pg/mL (10-60 pg/mL). A pituitary MRI was normal, and inferior petrosal sinus sampling was not consistent with a central ACTH source. A DOTA-TATE scan showed mediastinal lymphadenopathy and a 0.8cm area of uptake in the right breast. The patient was placed on ketoconazole and UFC normalized. Following biopsy, she underwent breast lumpectomy at an outside hospital, and pathology showed triple negative invasive carcinoma of the breast. Chemotherapy was initiated.However, her CS rapidly worsened: repeat UFC was 4867 μg, and ACTH was 369 pg/mL. Re-review of her pathology slides at our facility showed that the tumor stained negative for breast markers and positive for markers of NET and ACTH. Ki67 staining was approximately 30%. Chemotherapy for breast cancer was immediately stopped. A follow-up PET-CT continued to show uptake in the mediastinal lymph nodes. FNA of these lymph nodes revealed metastatic NET. In order to maximize control of her CS prior to chemotherapy, she underwent bilateral adrenalectomy (BLA). Afterwards, the patient received 10 cycles of chemotherapy with modified FOLFOX-7 for her NET. Thus far, the tumor burden appears stable, and she has been recommended to hold off on radiation therapy. She is currently taking replacement doses of hydrocortisone and fludrocortisone.Conclusion:In this challenging case, determination of source of ACTH hypersecretion led to an initial diagnosis of breast cancer. Primary breast carcinoma with neuroendocrine differentiation has been reported to show significant overlap in pathology with NET metastatic to the breast1. However, worsening of the CS in this case led to consideration of an alternative diagnosis, resulting in diagnosis of an ACTH producing NET metastatic to the breast. Prior to chemotherapy, she underwent BLA, which may lower morbidity and mortality associated with ACTH-dependent CS2, particularly given plan for further chemotherapy.Reference:1. Mohanty SK, Kim SA, DeLair DF, et al. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod Pathol. 2016;29(8):788-798. doi:10.1038/modpathol.2016.69.2.2. Morris LF, Harris RS, Milton DR, et al. Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing’s syndrome. Surgery. 2013;154(6):1174-1183; discussion 1183-1184.

Type 2 diabetes, breast cancer specific and overall mortality: Associations by metformin use and modification by race, body mass, and estrogen receptor status.

IntroductionWhile type 2 diabetes (T2D) has been associated with increased all-cause mortality among women diagnosed with breast cancer (BC), the association between T2D and breast cancer-specific (BCS) mortality is unresolved. The goal of this study was to examine the association between T2D and BCS mortality and examine the influence of metformin treatment on mortality rates.MethodsA retrospective cohort study was conducted between 2002 and 2008 at Emory University Hospitals among non-Hispanic black and white women who had confirmed diagnosis of stage I-III BC and known diabetes status (T2D: n = 73; non-T2D: n = 514). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsCompared to non-T2D patients, T2D women had almost a 2-fold increase in BCS mortality after adjusting for covariates (HR = 2.01; 95%CI = 1.02–3.98). Though attenuated, the increased hazard of death was also observed for all-cause mortality (HR = 1.74; 95%CI = 1.06–2.87). T2D patients who were not on metformin had substantially higher hazard of BCS mortality compared to non-diabetic patients (HR = 4.54; 95%CI = 1.98–10.44), whereas the association among T2D patients treated with metformin was weak (HR = 1.20; 95%CI = 0.36–3.97) and included the null.ConclusionsAmong women with BC, T2D is associated with increased BCS mortality. Metformin treatment for T2D during the initial diagnosis of BC may improve outcomes.

Evaluation of locoregional recurrence in patients with early breast carcinoma post-breast-conserving surgery with and without the use of preoperative chemotherapy

The effects of neoadjuvant chemotherapy in increasing the rate of conservative breast therapy and associated with reducing morbidity and better cosmetic has been fully acknowledged. Now, there are commonly used neoadjuvant chemotherapy for operable early breast carcinomas patients. Currently, neoadjuvant chemotherapy is used for locally advanced breast carcinoma, inflammatory breast cancer, and down staging of the large tumor to allow for breast conservative therapy. A prospective study performed in the department of surgery in Al-Sadder Medical City/Najaf city/Iraq, from the …….. of October 2015 to the 1st of October 2018, where 48 patients presented with a breast cancer diagnosis by clinical examination, Mammography, breast ultrasound, chest x-ray, bone scan, serum CEA, CA15_3 level, the initial diagnosis of breast cancer made by core needle biopsy. Breast saving surgery consisted of wide local excision with a safe margin with standard level I, II lymph node of axilla dissection. The resected specimen and lymph node was sent for histopathological examination; the size, width, length &amp;height dimension were recorded and the resection margin was recorded positive if close to 2mm and negative if &gt;2mm tumor-free margin. The 48 patients enrolled in this study with a mean age at diagnosis of 44.6 ± 8.4 years. 34 patients received neoadjuvant chemotherapy, Locoregional recurrence reported in 4 patients (28.6%) not received neoadjuvant chemotherapy (P. value &lt; 0.001), the higher relapse rate was reported significantly in the cases aged more than 50 years compared to those aged 50 years or below (P. value = 0.05, significant). Neoadjuvant chemotherapy decreases the incidence of locoregional recurrence of early breast carcinoma after breast-conserving surgery.

Association between cancer-specific adverse event triggers and mortality: A validation study.

BackgroundAs there are few validated measures of patient safety in clinical oncology, creating an efficient measurement instrument would create significant value. Accordingly, we sought to assess the validity of a novel patient safety measure by examining the association of oncology‐specific triggers and mortality using administrative claims data.MethodsWe examined a retrospective cohort of 322 887 adult cancer patients enrolled in commercial or Medicare Advantage products for one year after an initial diagnosis of breast, colorectal, lung, or prostate cancer in 2008‐2014. We used diagnosis and procedure codes to calculate the prevalence of 16 cancer‐specific "triggers"–events that signify a potential adverse event. We compared one‐year mortality rates among patients with and without triggers by cancer type and metastatic status using logistic regression models.ResultsTrigger events affected 19% of patients and were most common among patients with metastatic colorectal (41%) and lung (50%) cancers. There was increased one‐year mortality among patients with triggers compared to patients without triggers across all cancer types in unadjusted and multivariate analyses. The increased mortality rate among patients with trigger events was particularly striking for nonmetastatic prostate cancer (1.3% vs 7.5%, adjusted odds ratio 1.96 [95% CI 1.49‐2.57]) and nonmetastatic colorectal cancer (4.1% vs 11.7%, 1.44 [1.19‐1.75]).ConclusionsThe association between adverse event triggers and poor survival among a cohort of cancer patients supports the validity of a cancer‐specific, administrative claims‐based trigger tool.

Abstract P2-13-13: For women with bone-only metastatic breast cancer, is there a benefit to primary prevention?

Abstract Background: The prognosis of patients with estrogen receptor positive (ER+) bone-only metastatic breast cancer (B-MBC) is good, with the average life expectancy extending years with contemporary management. In the general population, studies investigating the impact of screening programs designed to detect disease as early as possible in otherwise asymptomatic patients have consistently shown reduction in morbidity and mortality but outcomes among patients living with B-MBC has not been adequately addressed. This study aimed to investigate the rate at which patients with ER+ breast cancer metastatic only to bone underwent cholesterol, breast cancer, colon cancer, and lung cancer screening and to determine if this screening had any impact on overall survival and cause of death. Methods: We conducted a retrospective chart review of patients treated for ER+ B-MBC at the Lifespan Cancer Institute in Providence, RI between 1/1/15 and 5/31/18. Each patient’s medical records and tumor registry information were reviewed. Data on these patients’ disease history were collected along with data on cholesterol, breast cancer, colon cancer, and lung cancer screening. Descriptive statistics were calculated using STATA statistical software. Results: A total of 48 patients with ER+ B-MBC were identified. Median overall survival from initial diagnosis of breast cancer was 148 months; measured from the diagnosis of bone metastasis, it was 52.4 months. Twenty-nine out of the 48 patients received cholesterol screening (60%), 14/48 had mammograms (29%), and only 8/48 had colonoscopy (17%). No patients underwent screening lung CT (Table 1). Compared to those who did not undergo screening, patients who were screened for cholesterol had significantly longer median overall survival (175.4 vs 106 months, respectively, p=.02) and those undergoing mammogram had a trend towards longer survival (187 vs 131 months, p=.08). Screening was not associated with a difference in rates of death attributed to breast cancer. No deaths due to other malignancies were identified. Of those undergoing mammography, only one abnormal report was identified, and biopsy of the lesion was benign. Table 1: Rate of abnormal screening results, median overall survival from index diagnosis, and death from index breast cancer.Abnormal screening resultMedian OS (months)95% CIp valueDeath from IBCp valueCholesterolscreened18/25175.4135 - 2160.02**1/20.30not screened10668 - 1445/6Mammogramscreened1/14187116 - 2590.08*3/40.60not screened131101 - 1626/10OS=overall survival. CI=confidence interval. IBC=index breast cancer. ** = p &amp;lt; 0.05. *= p &amp;lt; 0.1 Conclusions: A large proportion of patients with B-MBC undergo primary preventative screening measures, and of these, cholesterol screening is the most common. Screening was associated with longer overall survival, but did not change the rates of death due to breast cancer. These results suggest that clinicians are offering screening to a subgroup of women who are healthy despite B-MBC. However, our data suggest there is little benefit to screening, and this should be addressed in a larger dataset. Citation Format: Kristina A Fanucci, Mary Anne Fenton, Christine Duffy, Camille Higel-McGovern, Don Dizon. For women with bone-only metastatic breast cancer, is there a benefit to primary prevention? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-13.

Abstract P6-06-04: Exploratory computational longitudinal analysis of mammographic microenvironment disruption preceding breast tumorigenesis

Abstract Despite an aggressive emphasis on screening mammography, there has been no change in the number of initial metastatic breast cancer diagnosis since 1975. Even more alarming is the lack of effective screening to differentiate dormant cancerous pathology that may spontaneously ignite into an aggressive metastatic cancer. In this context, screening mammography is ineffective and biased towards a reactive diagnosis, when cancer is already present. We seek to develop a predictive algorithm that is sensitive to currently undetectable alterations of the microenvironment that precede tumorigenesis. Histological features such as tissue disruption and loss of tissue homeostasis, which are critical early indicators of breast cancer, unfortunately fall well outside the detection abilities of a trained radiologist or current computer-aided detection/diagnostic methods. In a recent publication using a powerful wavelet-based multifractal image analysis method, we extracted quantitative metrics for tissue disruption from standard mammography, and inferred a correlation with loss of tissue homeostasis. The 2D Wavelet-Transform Modulus Maxima (WTMM) method was used to quantify density fluctuations from mammographic breast tissue via a statistical roughness exponent called the Hurst exponent (H). The two mammographic tissue radiological states, i.e., fatty and dense, are quantitatively characterized with this Hurst exponent: H&amp;gt;1/2 (correlated spatial density fluctuations) for dense tissue; and H&amp;lt;1/2 (anti-correlated spatial density fluctuations) for fatty tissue. However, tissue regions that are neither dense nor fatty, with H~1/2 (uncorrelated spatial density fluctuations), were found preferably in patients with tumorous breasts vs. normal breasts (p-value = 0.0006) [Marin et al. Medical Physics, 2017]. The underlying physical processes associated with a H=1/2 signature are those of randomness and disorganization. Indeed, incoherent angular motion and the consequential adoption of randomized cellular motility are associated with malignant growth in breast tissue. We hypothesize that this H~1/2 signature accompanies or even preceeds tumorigenesis. In an exploratory analysis aimed at verifying this hypothesis, we studied, for 22 breast cancer patients, the progression of healthy breast tissue microenvironment towards a disrupted state by performing a computational analysis of longitudinal sequences of mammograms multiple years prior to, and leading to diagnostic. Preliminary results indicate a measurable change in mammographic density fluctuations (and therefore, potentially loss of tissue homeostasis), between 1 and 3 years prior to radiologic detection / diagnostic. An eventual larger-scale clinical validation of such an analysis could lead to the routine implementation of predictive algorithms based on the multifractal characterization of tissue disruption that precedes tumorigenesis. Such predictive diagnostics empowers both patient and clinician to collaboratively assess all ramification of the disease and select optimal therapeutics. Citation Format: Andre Khalil, Brian Toner. Exploratory computational longitudinal analysis of mammographic microenvironment disruption preceding breast tumorigenesis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-06-04.

Prophylactic Mastectomy and Breast Reconstruction in Patients at High Risk for Breast Cancer

This paper summarizes key issues pertinent to oncologic and surgical outcomes of risk-reducing mastectomy and reconstruction. Among BRCA 1/2 mutation carriers who present with initial breast cancer, risk-reducing mastectomy in patients who are young at time of initial breast cancer diagnosis have the greatest absolute reduction in contralateral breast cancer risk associated with contralateral risk-reducing mastectomy. Although retrospective studies are suggestive of a survival advantage conferred by risk-reducing mastectomy in BRCA ½ carriers, additional research in the contemporary era of magnetic resonance screening is necessary. A wide variety of reconstructive options are available after risk-reducing mastectomy. Long-term patient-reported outcomes favor autologous tissue reconstruction techniques. The decision for risk-reducing surgery and mastectomy reconstruction in patients with increased genetic propensity for breast cancer is multifaceted, with multiple factors pertinent to consideration including type of mastectomy, timing, and method of reconstruction. Shared informed decision making is critical to optimize outcomes. Appropriate patient counseling based on growing evidence regarding patient-reported outcomes should be provided in order to tailor therapeutic recommendations.