Diagnosis Of Metastatic Breast Cancer Research Articles

373P - Administration of chemotherapy for metastatic breast cancer near the end of life: A population registry study

BackgroundThe majority of patients with metastatic breast cancer (MBC) receive non-targeted cytotoxic chemotherapy during their disease trajectory. Its use however near the end of life has not been extensively studied and it’s possible that patients with advanced disease may be exposed to unnecessary aggressive treatment. MethodsPatients who were diagnosed with MBC in 2010-2015 were identified from the Stockholm-Gotland Breast Cancer Registry. Data regarding tumor characteristics, date of MBC diagnosis and death were collected from the registry. Data on chemotherapy use during the final month of the patient’s life, type of chemotherapy regimen used and albumin levels – a surrogate marker for performance status – were collected from individual patient files. Analysis of overall survival of the entire cohort was made in order to estimate contemporary survival of MBC patients. ResultsIn total, 1571 patients were identified. Out of 1559 patients included in the survival analysis, there were 1357 deaths and 202 patients still alive. Chemotherapy during the last month of life was given to 23.2% of the patients, more commonly to patients ≤60 years old (35.6% versus 18.5%, p<0.001). A new treatment regimen was initiated in 8.4% of patients. Both albumin (OR 0.95, 95% CI 0.92 – 0.98, p=0.002) and age at the time of diagnosis (OR 1.04, 95% CI 1.02 – 1.05, p<0.001) predicted the administration of chemotherapy. The most commonly used chemotherapeutic was capecitabine (24.8%), followed by paclitaxel (14.6%) and vinorelbine (9.8%). After a median follow-up of 73.4 months, median overall survival in the entire cohort was 16.73 months (95% CI 15.22–18.24); patients ≤60 years-old had better median survival compared to older ones (24.83, 95% CI 20.61-29.05 versus 13.86 months, 95% CI 12.72-15.74; p<0.001). ConclusionsChemotherapy use near the end of life was common, especially among younger patients. Median overall survival at the population level is considerably worse as compared to results from randomized trials. This may reflect on the differences in patient characteristics and completeness of registry data, which include patients that were never treated for MBC. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureJ. Bergh: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Sanofi-Aventis; Honoraria (self): UpToDate. T. Foukakis: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Novartis; Honoraria (self): UpToDate. All other authors have declared no conflicts of interest.

Outcome and feasibility of palliative chemotherapy in very elderly patients with metastatic breast cancer.

In the Netherlands, approximately 1300 women aged ≥75years die every year of metastatic breast cancer (MBC). Data on palliative chemotherapy (CT) in very elderly patients are rare, and prospective studies appeared cumbersome. Therefore, we retrospectively analyzed the outcome and feasibility of chemotherapy in elderly MBC patients. Records of all patients with MBC aged ≥75years who received first-line palliative chemotherapy between January 2000 and December 2014 at two large teaching hospitals in the Netherlands were reviewed. We registered patient and tumor characteristics together with data on previous adjuvant treatment, palliative endocrine treatment, comorbidities, clinical benefit (defined as ≥6months progression-free survival), toxicity, and the reason for stopping chemotherapy. Patients with progressive disease (PD) or death within 30days after starting CT were censored from analysis. A total of 54 patients with a median age of 77.6years (range 75-90) were treated with palliative chemotherapy for MBC. Of them, 20 patients (37%) were aged≥80years. There was clinical benefit in 28 patients (52%). Median progression-free survival and median overall survival were 6.0 and 14.0months, respectively. One year after the diagnosis of MBC, 27 patients (50%) were still alive and 15 patients (28%) lived longer than 2years. Reasons for stopping CT were progressive disease (n=32) or toxicity (n=13). Most patients (n=48) died of MBC while two patients died of toxicity. In selected patients with MBC aged 75years or older, single-agent palliative chemotherapy is feasible and may have clinical benefit.

Metastatic Breast Cancer as a Chronic Disease: Evidence-Based Data on a Theoretical Concept

Background: We challenge the concept of metastatic breast cancer (MBC) as a chronic disease. Methods: We analyzed an unselected cohort of 367 patients who were diagnosed with MBC over a 22-year period (1990–2011). Results: In order to create a “chronic disease subgroup”, we separated those patients from the entire cohort in whom systemic therapy was not applied after the diagnosis of MBC (n = 53; 14.4%). Three hundred fourteen patients (85.6%) comprised the “chronic disease subgroup”. The vast majority of those patients (89.8%) died of progressive disease after a median metastatic disease survival (MDS) of 25 months. Twenty patients (6.4%) died of non-MBC-related causes (MDS 38.5 months). Approximately 1 in 4 patients (26.8%) died within the first year after the MBC diagnosis. The 3- and 5-year MDS rates were 35.4 and 16.2%, respectively. Only 12 patients (3.8%) were exceptional survivors (MDS >10 years). Conclusion: The term “chronic disease” might be appropriate in selected MBC cases, bringing MBC into alignment with “classical” chronic diseases such as diabetes and hypertension. However, most cases display fundamental differences with regard to temporal progression and above all the case fatality rate. More than 90% of patients in the “chronic disease subgroup” died of the disease with a MDS of 2–3 years (even those who underwent systemic palliative therapies). Doctors and patients might understand the term “chronic disease” differently. The term must be used sparingly and explained carefully in order to create a common level of communication based on a shared understanding which avoids awakening false hopes and fostering misleading expectations.

Real-world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer.

Fulvestrant monotherapy is approved for postmenopausal women with hormone receptor-positive, metastatic breast cancer (MBC) who progressed following antiendocrine therapy, or those with hormone receptor-positive, human epidermal receptor 2-negative advanced breast cancer (BC) not previously treated with endocrine therapy (ET). However, real-world data are lacking. Retrospective reviews of 10 United States community oncology practices identified patients diagnosed with MBC between 1 January 2011 and 31 December 2015 who received fulvestrant as the first ET, either as initial therapy for metastatic disease or after progression following one line of chemotherapy. Endpoints were progression-free survival (PFS) and overall survival (OS). Patients were classified as ET-naïve or by relapse status following adjuvant ET ("early" recurrence during or ≤12months of completing adjuvant ET, or "late" >12months after completing adjuvant ET). Outcomes were evaluated using Kaplan-Meier methods. Among 121 patients, median PFS (95% confidence interval) was 8.3months (4.8-12.3) for early relapse, 15.4months (10.2-21.2) for late relapse, and 18.7months (10.1-20.8) among ET-naïve patients (P=.018). Median OS was 39.8months (25.0-55.1) for early relapse and 61.4months (47.1-61.4) for late relapse, but was not reached (NR; 55.6-NR) for ET-naïve patients (P=.002). Fulvestrant monotherapy as the first ET after MBC diagnosis demonstrates PFS comparable to clinical study results; outcomes appeared better in patients without prior ET exposure and in patients with disease recurrence >12months following adjuvant ET. These findings support fulvestrant monotherapy in patients with hormone receptor-positive MBC.

Radiological complete remission in HER2-positive metastatic breast cancer patients: what to do with trastuzumab?

Patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab may experience durable tumor response for many years. It is unknown if patients with durable radiological complete remission (rCR) can discontinue trastuzumab. We analyzed clinical characteristics associated with rCR and overall survival (OS) in a historic cohort of patients with HER2-positive MBC and studied the effect of stopping trastuzumab in case of rCR. We included patients with HER2-positive MBC treated with first or second-line trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Data were collected from medical records. We used multivariable regression models to identify independent prognostic factors for rCR and OS. Time-to-progression after achieving rCR for patients who continued and stopped trastuzumab, and breast cancer-specific survival were also evaluated. We identified 717 patients with a median age of 53years at MBC diagnosis. The median follow-up was 109months (IQR 72-148). The strongest factor associated with OS was achievement of rCR, adjusted hazard ratio 0.27 (95% CI 0.18-0.40). RCR was observed in 72 patients (10%). The ten-year OS estimate for patients who achieved rCR was 52 versus 7% for patients who did not achieve rCR. Thirty patients with rCR discontinued trastuzumab, of whom 20 (67%) are alive in ongoing remission after 78months of median follow-up since rCR. Of forty patients (58%) who continued trastuzumab since rCR, 13 (33%) are in ongoing remission after 68months ofmedian follow-up. Median time-to-progression in the latter groupwas 14months. Achieving rCR is the strongest predictor for improved survival in patients with HER2-positive MBC. Trastuzumab may be discontinued in selected patients with ongoing rCR. Further research is required to identify patients who have achieved rCR and in whom trastuzumab may safely be discontinued.

LPTO-08. INTRATHECAL TRASTUZUMAB PLUS/MINUS IT TOPOTECAN FOR PATIENTS WITH HER2+ BREAST CANCER AND LEPTOMENINGEAL METASTASIS

BACKGROUND: Leptomeningeal metastasis (LM) is an aggressive complication of cancer. No standard therapies exist, although at our institution we commonly use IT topotecan in good-risk patients. We report our experience in patients with HER2+ breast cancer (BC) LM treated with intrathecal (IT) trastuzumab +/- IT topotecan. METHODS: We retrospectively reviewed records of patients managed with IT trastuzumab at MD Anderson Cancer Center from 2016–2019. Demographics, clinical course, and outcomes data (Kaplan-Meier) were collected and analyzed. RESULTS: 14 female patients (median age 49, range 33–67) with HER2+ BC (29% hormone receptor (HR) positive, 71% negative) were treated with IT trastuzumab (titrated to 40 mg -100 mg/week); 8 (57%) received concurrent IT topotecan. LM diagnosis was made in 64% by MRI alone, and 36% by both MRI and CSF cytology; 79% had brain metastases (BM), and of those, 55% (6/11) had active BM at LM diagnosis; 57% received WBRT prior to initiation of IT therapy. Median KPS was 90 (range, 60–100). Of those with initially positive cytology, 50% (4/8) converted to negative during treatment. MRI findings improved in 79%; 79% were symptomatic at diagnosis (most commonly ataxia, cranial neuropathy, headache); 70% (7/10) had symptom improvement on IT therapy. The only IT-associated symptom reported was mild nausea that occurred in 29%. Median time from diagnosis of metastatic BC was 10.7 mos. (range 0–83 mos); 36% had active extra-CNS disease and 86% received concurrent systemic therapy; 57% underwent change in systemic therapy during IT treatment; 91% were progression-free at 6 months, 32% at 24 months. Median overall survival from LM diagnosis was 24.7 months (95% CI 10.7, NR). CONCLUSIONS: IT trastuzumab is a safe and promising therapy for patients with HER2+ BC and LM. Dual IT therapy with trastuzumab and topotecan was well-tolerated and warrants further investigation in a larger study.

Treatment patterns, survival and economic outcomes in Medicare-enrolled, older patients with HR+/HER2− metastatic breast cancer

Background: Endocrine therapy (ET) remains a foundation of systemic therapy for HR+/ HER2− metastatic breast cancer (MBC), although chemotherapy (CT) is used in select patients. In this “real-world” study, we explored treatment patterns, health care resource use (HCRU), costs, adverse events (AEs) and overall survival (OS) in Medicare-enrolled, older patients with HR+/HER2− MBC.Methods: Patients with HR+/HER2− MBC (2007–2011) and aged >66 years were retrospectively analyzed using the SEER–Medicare data. Treatment patterns, HCRU, costs, AEs and OS after MBC diagnosis through end of study period (31 December 2013) were examined using descriptive and multivariable analyses.Results: Among 3622 eligible patients, ET was the most common treatment (77%), followed by CT (50%), radiation (48%) and surgery (19%). The proportion of patients treated with ET monotherapy decreased across therapy lines, from 74% in first line (1 L) to 35% in 4 L. The total number of unique therapy regimens used was 181 in 1 L, 171 in 2 L, 128 in 3 L, and 95 in 4 L. The median OS from MBC diagnosis was 25.3 months (95% CI, 24.0–26.7). In multivariable analyses, receipt of CT and combination CT + ET (versus ET monotherapy) in 1 L, metastatic disease at initial diagnosis, larger tumor size, and presence of visceral and brain metastases at MBC diagnosis significantly predicted receipt of 2 L therapy.Conclusions: ET was the most common first-line treatment for study patients, but its use decreased gradually in the subsequent lines. The heterogeneity in the treatment selection highlights a lack of consensus for the management of HR+/HER2− MBC in routine practice.

Diagnosis and Management of Metastatic Breast Cancer During Pregnancy by a Multidisciplinary Team: A Case Report

Background: When breast cancer is diagnosed during pregnancy or within the first year after delivery, the condition is named as pregnancy-associated breast cancer (PABC). Breast cancer during pregnancy is a devastating situation for the patient, her family, and the medical team. Providing guidance for diagnosis and treatment of PABC, we report a case along with review of the literature.Case presentation: Here we present a 31-year-old pregnant woman with low back pain who was referred to the gynecology ward. She was at 25 weeks and 6 days pregnancy. After workup, it was discovered that she had a lytic lesion in her spine. Further workup revealed that she had metastatic breast cancer with the pathology of invasive ductal carcinoma. After consultation with a multidisciplinary team (a gynecologist, an oncologist, a radiotherapist, a hematologist-oncologist, and a neurosurgeon), we terminated the pregnancy and put her on radiotherapy for the spine metastasis and systemic therapy. Also, we reviewed 36 pregnant patients with primary or recurrent breast cancer who were managed with outpatient chemotherapy, surgery, or surgery plus radiation therapy. Care was provided by medical oncologists, breast surgeons, and perinatal obstetricians. Conclusion: Since there are no sufficient data in the literature to guide the development of standard protocols for management of PABC patients (specially in metastatic disease), pregnant women must be followed up by a multidisciplinary team, and each case should be managed considering the gestational age and the stage of cancer.

Risk stratification based on a prognostic factor index among patients with HR+, HER2- MBC.

e12516 Background: Patient and tumor characteristics, such as tumor grade (TG), site of metastases, hormone receptor status, and endocrine resistance, affect the prognosis for patients (pts) with HR+, HER2- metastatic breast cancer (MBC). This study explored the impact of multiple clinical prognostic factors on pt overall survival (OS) and real-world progression-free survival (rwPFS). Methods: This retrospective study used electronic health record (EHR) data of US pts from a network of community oncology practices maintained in the Vector Oncology Data Warehouse from 1/1/2008 to 4/30/2017. Eligibility included HR+, HER2- MBC diagnosis in 2008 or later and prior systemic therapy for MBC. An index variable was created to assess the effect of multiple clinical prognostic factors collectively, including liver metastases (LM), primary endocrine resistance (PER) (Cardoso F et al. 2018), negative progesterone receptor (PR-) status, and high TG. Pts were grouped based on the number of prognostic factors present at MBC diagnosis: 0, 1, and 2+. Differences in rwPFS and OS from start of first line therapy were evaluated by Kaplan-Meier method and multivariable Cox proportional hazards regression. Results: Eligible pts (n=378) had a mean age of 60.3 years. Among these 57.1% were white, 36.5% were de novo metastatic, 22% had LM, 27.2% had high TG, and 27.1% were PR- at baseline. Among all pts, 170 (45%) had received endocrine therapy as first-line treatment, followed by chemotherapy (28%), CDK4 &amp; 6 inhibitor (17%), or other anti-cancer treatment (9%). After adjustment, rwPFS and OS were significantly (p&lt;.05) shorter in pts with 1 and 2+ clinical prognostic factors compared to pts with none (Table). Conclusions: Among pts with HR+, HER2- MBC, these data demonstrate the heterogeneity in pt survival outcomes depending on the presence and number of prognostic factors. Further research should explore the collective importance of these prognostic factors in treatment decisions. [Table: see text]

Gaps in metastatic breast cancer patient knowledge and understanding in Mexico.

1090 Background: Among patients with metastatic breast cancer (MBC), there is paucity of data regarding knowledge and understanding about disease stage and goals of treatment. The limited evidence shows that up to 40% of MBC patients ignore their stage and reports inadequate educational resources and support. Aim: To assess MBC patients’ knowledge of their disease and satisfaction with the medical information received. Methods: 185 patients diagnosed with MBC who attended follow-up medical appointments at INCan from June to December 2018 were asked to complete a survey to assess their knowledge on MBC curability, subtype, topics reviewed with the oncologist, need of additional information regarding MBC and satisfaction with the quality of the information they received. Clinical data was obtained from the medical records. Descriptive statistics were applied, and the association between qualitative and quantitative variables was assessed with the Chi square test and the Mann Whitney U test, respectively. This study was supported by the SPARC mBC Challenge. Results: Only 52% of patients knew that their disease is not curable, while 31% were not sure and 17% thought it was curable. 82% ignored their MBC subtype and 81% reported to want more information about their cancer. 64% scored their satisfaction with the provided information ≥9 (out of 10), and 74% stated that their most helpful source of information was the medical staff. A statistically significant association was found between the perception of the impossibility of curing MBC and better patient satisfaction (p = 0.038). Likewise, better patients’ satisfaction was associated with older age (p = 0.002), longer time since initial diagnosis (p = 0.018) and since diagnosis of MBC (p = 0.014). Conclusions: Our results dramatically illustrate the lack of understanding patients have regarding their cancer, even when reporting high satisfaction with the received information, and identify a critical need for improvement of healthcare providers’ communication skills. Directed efforts should be implemented to enhance patients’ comprehension to promote their participation in decision-making processes, adherence and, ultimately, outcomes.

Long-Term Survival and Cure in Distant Metastatic Breast Cancer

Background: Previous data showed that distant metastatic breast cancer (MBC) might be curable in up to 3% of the cases in selected patients, mostly young, with good performance status and with low-volume metastatic disease, mainly by an aggressive multidisciplinary approach including aggressive combination chemotherapy regimens. These long-lasting responses question the belief that MBC is wholly incurable. This study evaluates the rate of long-term survivors and potentially cured patients in an unselected cohort of MBC patients. Methods: We analyzed the data from 342 patients in whom distant MBC was diagnosed from 1990 to 2011. For this study, we defined a metastatic disease survival (MDS) of 9 years as inclusion criterion for long-term survivorship. Results: Eighteen patients (5.3%) were long-term survivors (MDS: 126 months; range, 108–300 months). The rate of long-term survivors was equally distributed over time (1990–1999: 4.3% vs. 2000–2011: 5.9%, p = 0.63). Compared to patients who had a lower MDS, long-term survivors had significantly more often primary MBC (p = 0.005) and hormone receptor-positive carcinomas (p = 0.015). Age at MBC diagnosis, presence of visceral metastases, and limited number of metastatic sites at the time of MBC diagnosis appeared to have no significant impact on long-term survival. Long-term survival was not associated with the use of chemotherapy (50.0% vs. 65.7% in the control group, p = 0.21). Eight patients (2.3%) developed a complete remission and presented with no evidence of disease at the time of last follow-up (MDS: 234.5 months). Conclusion: Since long-term survivors in MBC comprise a relatively heterogeneous group, the factors that lead to the quite rare and felicitous case of long-term survival or even cure can hardly be evaluated systematically. Some patients may be considered cured of their disease. This fraction may be small, but the chance of survival, and even of cure, truly exists. Perhaps we must accept that the factors contributing to long-term survival remain an enigma. It appears, however, that aggressive chemotherapy is not the only key factor to long-term remission.

Noncompliance with palliative systemic therapy in patients with distant metastatic breast cancer: a blind spot for oncologists?

The goal of our study was to provide a general overview of noncompliance with palliative systemic therapy in distant metastatic breast cancer (MBC). We analyzed an unselected cohort of 339 patients who were diagnosed with MBC over a 22-year period (1990-2011, age restriction: ≥ 85years old). Forty patients (11.8%) rejected the offered or recommended systemic therapy (age distribution of this noncompliance subgroup: ≤60years at MBC diagnosis: 7.9%; 60-70years: 13.2%; > 70years: 15.6%). The rate of noncompliance was equally distributed over time (1990-1999: 12.2% vs. 2000-2011: 11.5%, p = 0.87). Compared to patients who had received palliative antineoplastic systemic therapy, those who remained untreated were significantly older (70 vs. 61years, p = 0.015), had shorter metastatic disease survival (2 vs. 27months, p < 0.001), had more often an aggressive tumor subtype (hormone-receptor negative carcinomas: 48.7% vs. 22.2%, p < 0.001), and had more often secondary MBC (95.0% vs. 73.6%, p = 0.001). Although the high rate of noncompliance in the subgroup of elderly patients was not unexpected, it is noticeable that even in the subgroup of patients who were younger than 60years, approximately 8% also rejected any systemic therapy before a MBC-related death occurred This group of younger women rarely had any relevant comorbidities, were potential candidates for chemotherapy and knowingly declined the therapy options. Such patients are never or seldom seen by oncologists in their daily practice and therefore play a minor role in their personal perception of disease. Nevertheless, these under-reported cases make up a significant proportion of MBC.

Treatment Patterns and Outcomes Associated With Palbociclib Plus Letrozole for Postmenopausal Women With HR+/HER2− Advanced Breast Cancer Enrolled in an Expanded Access Program

PurposeTo evaluate treatment patterns and clinical outcomes of patients who received palbociclib in combination with letrozole in any line of therapy for treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer in an expanded access program (EAP) in the United States. Patients and MethodsA retrospective chart review study was conducted of patients previously enrolled in the palbociclib EAP. Complete data from time of initial diagnosis of metastatic breast cancer until date of chart abstraction were obtained. Clinical outcomes as assessed by site investigators included clinical benefit rate, progression-free survival, and overall survival. Survival was descriptively assessed using Kaplan-Meier methods. ResultsOf 238 patients enrolled in the EAP, data from 126 patients were included. Median age was 62.5 years at EAP enrollment; 25% had de novo metastatic disease. Visceral disease was present in 71% of patients. The disease of most patients was heavily pretreated; nearly 60% of patients had received 3 or more prior lines for metastatic disease before initiating palbociclib + letrozole therapy. Most patients (87%) had received prior endocrine therapy, and 68% had received prior chemotherapy for metastatic disease. Patients with prior endocrine therapy for metastatic disease had a clinical benefit rate of 30%, while those with prior chemotherapy had a 26% clinical benefit rate. Patients receiving 2 or more prior lines had 6- and 12-month progression-free survival rates of 35% and 21%, respectively, and 12- and 24-month overall survival rates of 62% and 35%, respectively. ConclusionMost patients derived benefit from palbociclib + letrozole treatment despite having received multiple prior treatment lines for metastatic disease.

Central Nervous System Metastasis in Patients with HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from SystHERs.

Patients with HER2-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs). SystHERs (NCT01615068) was a prospective, U.S.-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PRO). Among 977 eligible patients enrolled (2012-2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor-negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis [median overall survival (OS) 30.2 and 38.3 months from MBC diagnosis, respectively] versus no CNS metastasis [median OS not estimable: HR 2.86; 95% confidence interval (CI), 2.05-4.00 and HR 1.94; 95% CI, 1.52-2.49]. Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment. Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.

Overexpression of PIMREG promotes breast cancer aggressiveness via constitutive activation of NF-κB signaling.

BackgroundIt is well-established that activation of nuclear factor-kappa B (NF-κB) signaling plays important roles in cancer development and progression. However, the underlying mechanism by which the NF-κB pathway is constitutively activated in cancer remains largely unclear. The present study aimed to investigate the effect of PICALM interacting mitotic regulator (PIMREG) on sustaining NF-κB activation in breast cancer.MethodsThe underlying mechanisms in which PIMREG-mediated NF-κB constitutive activation were determined via immunoprecipitation, EMSA and luciferase reporter assays. The expression of PIMREG was examined by quantitative PCR and western blotting analyses and immunohistochemical assay. The effect of PIMREG on aggressiveness of breast cancer cell was measured using MTT, soft agar clonogenic assay, wound healing and transwell matrix penetration assays in vitro and a Xenografted tumor model in vivo.FindingsPIMREG competitively interacted with the REL homology domain (RHD) of NF-κB with IκBα, and sustained NF-κB activation by promotion of nuclear accumulation and transcriptional activity of NF-κB via disrupting the NF-κB/IκBα negative feedback loop. PIMREG overexpression significantly enhanced NF-κB transactivity and promoted the breast cancer aggressiveness. The expression of PIMREG was markedly upregulated in breast cancer and positively correlated with clinical characteristics of patients with breast cancer, including the clinical stage, tumor-node-metastasis classification and poorer survival.InterpretationPIMREG promotes breast cancer aggressiveness via disrupting the NF-κB/IκBα negative feedback loop, which suggests that PIMREG might be a valuable prognostic factor and potential target for diagnosis and therapy of metastatic breast cancer.FundThe science foundation of China, Guangdong Province, Guangzhou Education System, and the Science and Technology Program of Guangzhou.

Lateral rectus muscle biopsy as diagnosis of unknown metastatic breast cancer

The case concerns a 58 year-old female with no medical history of interest who consulted due to binocular diplopia of one week onset. It was associated with costal pain, dyspnoea, intense asthenia and weight loss of 2 months onset. In the blood analysis in the Emergency Department it showed hypercalcaemia, renal failure, and bicytopenia. The chest x-ray showed lytic bone lesions that initially lead to multiple myeloma with extra-osseous involvement. In addition to the corresponding study, in case of horizontal diplopia, a cranial CT scan without contrast was performed where an adjacent lesion to the lateral wall of the left orbit is observed. This was of soft tissue density, and included the external rectus muscle that exerts a mass effect on the optic nerve by displacing it medially. Many lytic bone diffuse lesions with salt and pepper pattern were found in the calotte. A rectus lateral muscle and bone biopsy of the sacral wing was performed, resulting in metastasis of carcinoma compatible with mammary origin. An atypical case is presented of horizontal diplopia in the context of a patient with a severe constitutional picture with no established diagnosis, in which the biopsy of the lateral rectum was key to the confirmation diagnosis.

Abstract P2-08-48: Features associated with long-term survival in metastatic breast cancer

Abstract Background: 5-10% of women with metastatic breast cancer (MBC) survive ≥5 years. Predictors of long-term survival are not clearly elucidated. We used data from 122 long-term MBC survivors (≥5-year survival from date of MBC diagnosis) and 191 short-term MBC survivors (≤2-year survival from date from MBC diagnosis) to identify clinico-pathologic and socioeconomic features associated with MBC survival. Methods: Women initially diagnosed with breast cancer (BC) in or after 1999, and diagnosed with MBC at Magee Women's Cancer Program of UPMC were included (N=313). Data abstracted from medical records included: stage at initial BC diagnosis, body mass index (BMI), Charlson Comorbidity Index (CCI), age, menopausal status at initial BC diagnosis, tumor receptor status at initial BC diagnosis, site of initial metastases, time to recurrence between initial diagnosis and MBC, household income, race, employment status, and partner status. Differences between groups were assessed using t-tests and Chi-square or Fisher's exact tests. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression models. Results: Long-term survivors were significantly (P&amp;lt;0.05) younger, had more ER positive, PR positive, and Her2 positive disease, lower CCI, more often premenopausal at initial diagnosis, lower rates of visceral metastases, higher household income, and more often partnered than short-term survivors. The association of premenopausal status at initial diagnosis with long-term survival remained significant after adjustment for stage at initial diagnosis, tumor receptor status, and CCI (OR: 1.96, 95% CI 1.02- 3.79). Long-term term survivors were also significantly more often diagnosed with de novo MBC compared to short-term survivors. The association of de novo MBC with long-term survival remained significant after adjustment for age, tumor receptor status, and CCI (OR: 3.0, 95% CI 1.6-5.4). Time to recurrence between initial diagnosis and MBC, BMI, race, and employment status were not associated with survival. Conclusions: Diagnosis of de novo MBC, ER-, PR- and/or Her2-positive primary tumor, lower rates of visceral metastases, higher household income, younger age, lower CCI, premenopausal status, and having a partner are associated with long-term survival after diagnosis of MBC. This is one of the first studies to show a survival benefit in MBC for patients with de novo MBC, premenopausal status at initial diagnosis, positive partner status, and higher household income. Citation Format: Klar NJ, Rosenzweig M, Diergaarde B, Brufsky A. Features associated with long-term survival in metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-48.

Abstract P2-08-66: Outcomes among metastatic breast cancer patients with characteristics that confer a less favorable prognosis

Abstract Background: Recent advances in the treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) have contributed to increased overall survival (OS). Despite advances, MBC remains incurable and there is a subset of patients with clinical features that are associated with poorer prognosis. This study described the patient characteristics, treatment patterns, and outcomes of a cohort of US patients with HR+, HER2- MBC as a function of various factors associated with poor prognosis, including presence (vs. absence) of liver metastases (LM). Methods: This retrospective study used US community oncology electronic health record data from the Vector Oncology Data Warehouse. Eligible women who received systemic treatment for MBC, had a diagnosis of MBC in 2008 or later, and had completed at least three Patient Care Monitor (PCM) surveys, (a patient-reported outcomes survey collected as a part of clinical care), were included. OS was measured from the start of the first three regimen-based lines (1L, 2L and 3L) of treatment; patients without evidence of death were censored at the last observed visit. The statistical significance of differences in categorical and continuous variables between LM positive (LM+) and LM negative (LM-) were evaluated with chi-square (X2) tests, and t-tests, respectively. Kaplan-Meier and Cox analyses were applied to evaluate differences in OS by LM status and by line of therapy at the start of MBC treatment (unadjusted for treatment). Results: A total of 378 women, 98.4% residing in the South and 40.5% African-American, were included; 295 (78.0%) were LM- at the time of diagnosis. Following 1L, approximately 82.8% and 60.8% of patients received 2L and 3L, respectively. Patients with a LM+ status had a lower mean age (mean: 57.2, SD: 13.8 vs. 61.2, 13.1; p=0.016) and a higher percentage had a grade 3 tumor (36.1 vs. 24.7%; p=0.039) compared to patients with LM-status. Table 1 shows the OS results for 1L-3L. For all 3 lines, median OS for LM+ was shorter than the LM- median OS. LM+ patients had a poorer prognosis as they were more likely to have an OS event across 1L-3L compared to LM- patients. Conclusions: Among this community oncology cohort, median OS in 1L was 14 months shorter in LM+ patients compared to LM- patients. It is important to note that the sample size and selection criteria may limit generalizability of these results. Despite progress in treating women with MBC, treatment options are lacking for patients with less favorable prognosis, including those with LM. Other potential indicators of poor prognosis, such as high tumor grade, are being explored. Table 1.OS (months) by regimen-based line of therapy Measure Liver Mets (LM+) No Liver Mets (LM-) HR p-value 1L, # of Events/ # of Patients55/83168/295 Median (95% CI)23.9 (15.5-28.6)35.2 (30.1-42.3) &amp;lt;0.0001* Cox Hazard Ratio 1.93&amp;lt;0.0001 2L, # of Events/ # of Patients48/72149/241 Median (95% CI)16.6 (12.0-22.6)24.2 (21.3-29.0) 0.002* Cox Hazard Ratio 1.490.040 3L, # of Events/ # of Patients35/52118/178 Median (95% CI)11.5 (7.0-21.0)17.4 (14.7-20.0) 0.038* Cox Hazard Ratio 1.540.060CI=Confidence Interval; *p-value was derived using log rank test. Citation Format: Saverno K, Cuyun Carter G, Dufour R, Price G, Li L, DeLuca A, Nash Smyth E, Battiato L, Gable J, Walker MS, Huang Y-J, Hannas S, Schwartzberg LS. Outcomes among metastatic breast cancer patients with characteristics that confer a less favorable prognosis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-66.

Abstract P4-01-06: Comparison of tumor genotyping and cell-free circulating tumor DNA sequencing in metastatic breast cancer patients and their utility in the selection of matched therapy

Abstract Background: Oncogenic mutations are potential targets for therapeutic intervention in metastatic breast cancer (MBC). While tumor genotyping (TG) has been viewed as the gold standard for identifying oncogenic mutations, cell-free circulating tumor DNA (cfDNA) is emerging as an alternate technique. We previously reported the selection of matched therapy targeted to an actionable mutation based on either TG or cfDNA testing (Vidula N, ASCO, 2018). Therefore, we are now comparing TG and cfDNA results in MBC patients undergoing both tests to examine their relative utility in the selection of matched therapy. Methods: Patients with MBC at an academic institution who underwent both TG (Next Generation Sequencing/NGS, institutional platform, 104 gene assay) and cfDNA testing (NGS/Guardant360, 73 gene assay) between 1/2016-10/2017 were identified. A chart review was conducted to identify tumor subtype, demographics, treatment, TG and cfDNA results, and clinical outcomes. The relative utility of these tests in the selection of matched therapy was determined, and linked with clinical outcomes (progression-free survival and overall survival). Results: Thirty patients who underwent both TG and cfDNA testing were identified. The median age was 60 years, the majority (97%) had hormone receptor (HR) positive/HER2 negative disease, and most patients had recurrent disease (83.3%) at MBC diagnosis. The median number of therapies prior to obtaining either test was 1 (cfDNA range 0-9, TG range 0-8). The majority had simultaneous cfDNA and tumor genotyping testing (83.3%) versus sequential testing (16.7%). Twenty-four (80%) patients had actionable mutations detected by cfDNA compared to 19 (63.3%) patients with actionable mutations detected by TG. The median number of actionable mutations detected by cfDNA was 2 (range 0-11) compared with a median of 1 (range 0-4) detected by TG. Failure of TG occurred in 2 of 30 patients (6.7%) but no test failures were seen with cfDNA. Eleven of 30 patients (36.7%) had ≥ 1 concordant mutation via cfDNA and TG. Altogether, 12 out of 30 (40%) patients received matched therapy, 5 of which were based on cfDNA actionable mutations alone (ESR1, ERBB2, CCND1, and PIK3CA), and 7 based on cfDNA and TG results (ESR1, PIK3CA, STK11, and BRCA). Twelve of 24 (50%) patients with actionable cfDNA mutations went on to receive matched therapy compared with 7 of 19 (36.8%) patients with actionable TG results. Matched therapies included SERDs, inhibitors of CDK 4/6, PI3K, mTOR, HER2 directed therapy, and DNA damaging chemotherapy. The impact of matched therapy on survival outcomes will be presented at the meeting. Conclusions: In patients undergoing both TG and cfDNA testing, both tests identify a significant cohort of HR+ MBC patients with actionable mutations, with greater detection of actionable mutations by cfDNA. Greater application of matched therapy occurred via cfDNA, which independently informed the selection of matched therapies. Further research is needed to prospectively evaluate the clinical utility of blood based genotyping assays versus TG for patients with MBC. Citation Format: Vidula N, Juric D, Niemierko A, Spring L, Moy B, Malvarosa G, Yuen M, Habin K, Shin J, Peppercorn J, Isakoff S, Ellisen L, Iafrate AJ, Bardia A. Comparison of tumor genotyping and cell-free circulating tumor DNA sequencing in metastatic breast cancer patients and their utility in the selection of matched therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-06.

Abstract P1-11-20: Patient reported supportive care needs in a dedicated advanced breast cancer center

Abstract Background: As of January 1st, 2017 nearly 154,794 women in the US will be living with metastatic breast cancer (MBC) and rates are expected to increase. Additionally, 58.3% of individuals with MBC, and their caregivers, believe that people with MBC have unique informational, emotional and physical needs that are unmet. However, there are still few research studies examining these needs. Methods: In October of 2016, the Koontz Center for Advanced Breast Cancer was established in Kansas City, MO. Supportive services assume a large role in this center to assist in caring for the whole person and improving quality of life. During the initial consult, the patient meets with the medical oncologist, psychologist, social worker, nutritionist, exercise physiologist and chaplain. All patients complete forms assessing multiple domains that may influence the patient's treatment and outcomes. We use the PROMIS (Patient-Reported Outcome Measurement Information System) measures to assess sleep, physical function, fatigue and pain interference, the Daily Spiritual Experience Scale (DSES) to assess spiritual concerns, the DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure-Adult to assess mental health concerns and Koontz Center forms to assess social work and nutritional concerns. The following data is from assessments collected through May of 2018. Results: Eighty-two individuals were included in the analysis. The mean age was 60.1 (SD=10.6) and 98% (n=80) were female. A majority were white, non-Hispanic (88%; n=71). Sleep related impairment was mild for 27 (33.8%) individuals, moderate for 22 (27.5%) and severe for 3 (3.8%). For physical function, 12 (14.8%) individuals had mild, 32 (39.5%) moderate and 19 (23.5%) severe impairment. Twelve (15%) individuals had mild, 25 (31.3%) moderate and 6 (7.5%) severe symptoms of fatigue. For pain interference, 14 (17.3%) individuals had mild, 24 (29.6%) moderate and 9 (11.1%) severe symptoms. The average DSES score was 12.6 (SD=6.8) out of 36 with lower scores indicating stronger spiritual satisfaction. The top three mental health concerns were anxiety (n=47; 58.8%), depression (n=40; 50%) and somatic symptoms (n=38; 47.5%). Seventeen percent (n=14) reported concern over weight and 30% (n=24) reported losing weight over the past two weeks. The top three areas individuals reported needing assistance in were finding financial resources (n=16; 20.5%), help at home (n=11; 14.1%) and insurance questions (n=10; 12.8%). The top four areas individuals reported needing support in were information on support groups (n=20; 25.6%), managing stress (n=20; 25.6%), coping with cancer diagnosis (n=14; 17.9%) and communicating with children about cancer (n=14; 17.9%). Also, 38% (n=28) endorsed wanting information about an advanced directive. Changes across age and symptom complexes were also noted and will be presented. Conclusion: The data indicate that there are a wide variety of physical, spiritual, nutritional, social and psychological concerns for those coping with a MBC diagnosis. Future treatment of those with MBC should integrate supportive services to address these symptoms. Citation Format: Geske SJ, Pluard TJ, Amazu C, Holden R. Patient reported supportive care needs in a dedicated advanced breast cancer center [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-20.