Standard Adjuvant Therapy Research Articles

Yoga versus massage in the treatment of aromatase inhibitor-associated knee joint pain in breast cancer survivors: a randomized controlled trial

Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with oestrogen receptor-positive, early-stage, and metastatic breast cancer. Although effective, the risk of falls due to AI-associated knee joint pain significantly increased. The aim of this study was to evaluate the therapeutic effects of yoga and massage on AI-associated knee joint pain. Breast cancer survivors were randomly assigned to a 6-week yoga intervention-2-week rest-6-week massage exposure (Yoga first, n = 30) or a 6-week massage intervention-2-week rest-6-week yoga exposure (Massage first, n = 30). Evaluations of the treatment efficacy were made at baseline, post-intervention, and post-exposure using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, plasma cytokine levels, and changes in meridian energy. The results showed that yoga, superior to massage intervention, significantly reduced AI-associated knee joint pain, as demonstrated by the WOMAC pain score. The yoga intervention improvements were also associated with changes in plasma cytokine levels and meridian energy changes. In conclusion, this study provides scientific evidence that yoga was more effective than massage for reducing AI-associated knee joint pain. Meridian energy changes may provide another scientific, objective, non-invasive way to monitor the therapeutic effects of yoga and investigate another alternative, complementary medicine.

Aggressive Recurrent Urachal Adenocarcinoma : A Case Report And Review Of The Literature

Recurrent urachal adenocarcinomas are rare. It is commonly associated with poor prognosis. A 51-year-old woman underwent a partial cystectomy for urachal cancer in 2014. She was well throughout follow-up with annual cystoscopies. She presented with a 1-month history of rapidly progressive suprapubic mass and hematuria. A contrasted computed tomography scan of the thorax, abdomen and pelvis showed a large mixed solid cystic tumour at the right lumbar region, suprapubic area and also at the pouch of Douglas. She refused surgical extirpation and now on chemotherapy. Urachal adenocarcinoma is rare, and resection is commonly advocated; usually, no standard adjuvant therapy is advocated. Recurrent cancers represent a management dilemma, and no standard follow-up protocols exist.
 Bangladesh Journal of Medical Science Vol.20(4) 2021 p.911-913

ADAPTlate: A randomized, controlled, open-label, phase III trial on adjuvant dynamic marker—Adjusted personalized therapy comparing abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy in (clinical or genomic) high-risk, HR+/HER2- early breast cancer.

TPS598 Background: The WSG ADAPT trial program addresses the individualization of (neo)adj. decision-making in EBC. The ADAPT umbrella trial established early predictive molecular surrogate markers for response after a 3-wk endocrine treatment (ET) to omit chemotherapy (CT) in a cohort of early high-risk HR+/HER2- pts. ADAPTlate seeks to improve adj. therapy for pts. at high risk for late disease recurrence, who completed definite locoregional therapy (with / without (neo-)adj. CT) and are under adj. ET. This high-risk population does not derive optimal benefit from standard ET, develops secondary ET resistance, and late recurrences. Methods: Prospective, multi-center, interventional, two-arm, open, randomized, controlled adj. phase III trial (NCT04565054) to investigate additional benefit from 2 years of the CDK4/6-inhibitor abemaciclib combined with ET compared to ET alone in pts. with high-risk HR+/HER2- EBC. Abemaciclib demonstrated to improve outcome in metastatic BC and even in EBC when given as part of primary therapy. Primary objective is to demonstrate superiority of iDFS of abemaciclib + ET vs. standard ET. Secondary objectives include OS, dDFS, occurrence of CNS metastases, QoL, and translational research. Recruitment started in 9/2020 to screen 1250 pts. and to randomize 903 pts. in a ratio 3:2. Until date of submission, 33 pts. were screened and 22 randomized. Pre-/postmenopausal pts. with histologically confirmed invasive HR+/HER2- EBC, 2-6 y after primary diagnosis, with either known high clinical risk (c/pN 2-3 OR high CTS score in pN 0-1 OR non-pCR after neoadj. CT in cN 1 or G3 tumors OR G3 and Ki-67 ≥ 40% in pN 0-1) or known high genomic risk (RS >25 in c/pN 0, RS >18 in c/pN 1 OR high risk Prosigna, EPclin or Mammaprint in pN 0-1) or intermediate clinical, but unknown genomic risk (luminal B-like (G3 or Ki-67 ≥20%) in c/pN 0-1 AND either RS >25 in c/pN 0 or RS >18 in c/p N1 in screening) will be eligible. Treatment duration is 2 years for the abemaciclib + ET (premenopausal: AI + GnRH) arm, followed by at least 3-6 years ET alone. Pts. in control arm will receive 5-8-years ET at investigator´s choice. ePROs are collected using CANKADO. Translational analyses: Exploratory tissue biomarker research to assess alterations in molecular markers. Liquid biopsies (CTC/ctDNA/ctRNA) will be assessed for mutations and gene expression relevant for HR+/HER2- EBC using an appropriate technology at time of testing. Conclusions: ADAPTlate seeks to evaluate whether Abemaciclib + ET is superior to ET alone in pts. with clinical or genomic high-risk EBC even 2-6 years after initial diagnosis. Translational research aims at assessing potential mechanisms of resistance to endocrine and/or CDK4/6 targeted therapy. Clinical trial information: NCT04565054.

EMonarcHER: A phase 3 study of abemaciclib plus standard adjuvant endocrine therapy in patients with HR+, HER2+, node-positive, high-risk early breast cancer.

TPS596 Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with high-risk characteristics has a high risk of disease recurrence. Novel therapeutic options for this population are urgently needed. Abemaciclib is an oral, selective, and potent CDK4 & 6 inhibitor administered on a continuous schedule which is approved for HR+, HER2- advanced BC (ABC) as monotherapy and in combination with endocrine therapy (ET). Abemaciclib combined with ET demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) in participants (pt) with HR+, HER2-, node-positive, high risk early breast cancer (EBC) and also clinical activity in HR+, HER2+ ABC. The eMonarcHER trial investigates whether abemaciclib plus ET will improve IDFS in pts with HR+, HER2+, node-positive, high risk EBC. Methods: eMonarcHER is a phase 3 global, randomized, double-blinded, placebo (PB)-controlled trial in participants with HR+, HER2+, node-positive, high risk EBC who have completed adjuvant HER2-targeted therapy (tx). Eligible participants are randomized 1:1 to receive either abemaciclib 150 mg twice daily or PB, plus standard ET. Study intervention period will be ≤26 cycles (approximately 2 years) followed by ≤8 years of ET as medically indicated. Participants must have undergone definitive surgery of the primary breast tumor and have high-risk disease. High-risk disease is defined as (i) detection of residual axillary nodal disease at the time of definitive surgery in participants with prior neoadjuvant (neoadj) tx; or (ii) in patients not receiving neoadj tx, must have either ≥4 pathologically positive axillary lymph nodes (pALNs), or 1-3 pathological pALNs and either: histologic Grade 2-3 and/or primary invasive tumor size ≥5 cm. Participants must have received either adjuvant pertuzumab plus trastuzumab with chemotherapy or adjuvant T-DM1. Stratification factors include treatment with neoadj tx, menopausal status, and region. The study is powered at approximately 80% to detect the superiority of abemaciclib plus ET over PB plus ET in terms of IDFS (as defined by the STEEP system) at a 1-sided α =.025 using a log-rank test. Assuming a hazard ratio of 0.73, this requires approximately 324 events at final IDFS analysis. Key secondary objectives include overall survival, distant relapse free survival, safety, pharmacokinetics, and patient-reported outcomes. The study is planned to start in March 2021. Approximately 525 centers in 23 countries plan to enroll ̃2450 participants. Clinical trial information: NCT04752332.

PROSPER: Phase III RandOmized Study Comparing PERioperative nivolumab versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN EA8143).

TPS4596 Background: There is no standard adjuvant systemic therapy that increases overall survival (OS) over surgery alone for non-metastatic RCC. Anti-PD-1 nivolumab (nivo) improves OS in metastatic RCC and is well tolerated. In mouse models, priming the immune system prior to surgery with anti-PD-1 results in superior OS compared to adjuvant dosing. Remarkable pathologic responses have been seen with neoadjuvant PD-1 in multiple ph 2 studies in bladder, lung and breast cancers. Phase 2 neoadjuvant RCC trials of nivo show preliminary feasibility and safety with no surgical delays. PROSPER RCC seeks to improve clinical outcomes by priming the immune system with neoadjuvant nivo prior to nephrectomy followed by continued immune system engagement with adjuvant blockade in patients (pts) with high risk RCC compared to standard of care surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is accruing pts with clinical stage ≥T2 or TanyN+ RCC of any histology planned for radical or partial nephrectomy. Select oligometastatic disease is permitted if the pt can be rendered ‘no evidence of disease’ within 12 weeks of nephrectomy (≤3 metastases; no brain, bone or liver). In the investigational arm, nivo is administered 480mg IV q4 weeks with 1 dose prior to surgery followed by 9 adjuvant doses. The control arm is nephrectomy followed by standard of care surveillance. There is no placebo. Baseline tumor biopsy is required only in the nivo arm but encouraged in both. Randomized pts are stratified by clinical T stage, node positivity, and M stage. 805 pts provide 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival at 5 years assuming the ASSURE historical control of ̃56% to 70% (HR = 0.70). The study is powered to evaluate a significant increase in OS (HR 0.67). Critical perioperative therapy considerations such as safety, feasibility, and quality of life metrics are integrated. PROSPER RCC embeds a wealth of translational studies to examine the contribution of the baseline immune milieu and neoadjuvant priming with anti-PD-1 on clinical outcomes. As of February 10, 2021, 704 patients have been enrolled (N = 805). Clinical trial information: NCT03055013.

Adult-onset acne: An expert consensus

Despite the increasing incidence of adult acne in recent times practical guidelines for management of these patients are lacking in India setup. Thus, to develop practical consensus-based recommendations on diagnosis and management of acne in adult patients an expert panel was finalized. The consensus was developed using Delphi method. Panel members were asked to complete two Delphi surveys one for diagnosis and another for management. Experts reached consensus on practical approach of diagnosis and management of patients with adult acne based on available evidence and their personal experience. Experts recommended that a holistic treatment approach consisting of standard therapy, adjuvant therapy and cosmetic use should be first choice treatment strategy in adult acne patients. Experts also commented that treatment choices should be individualized based on the specific characteristics of each patient and be tailored to suit this particular population.

Glycans unique to the relapse-prone subset within triple-negative breast cancer as revealed by lectin array-based analysis of surgical specimens.

Molecular and cellular characteristics of the relapse-prone subset within triple-negative breast cancer (TNBC) remain unclear. Aberrant glycosylation is involved in the malignant behavior of cancer cells. In the present study, we aimed to reveal glycan profiles unique to relapsed TNBC patients. Thirty TNBC patients who did not undergo neoadjuvant chemotherapy but postoperative standard adjuvant therapy from 2009 through 2016 at Juntendo Hospital were investigated. TNBC cells were resected from primary breast cancer sections of formalin-fixed surgical specimens using laser-assisted microdissection. The binding intensities of the extracted glycoproteins to 45 lectins were quantified using lectin microarray and compared between relapsed and non-relapsed patients. Immunohistochemical staining with TJA-II lectin in specimen sections was performed. Five patients relapsed during the follow-up (range 37-123 months). Lectin microarray analysis revealed that 7 out of 45 lectins showed significant differences in binding intensity between the relapsed and the non-relapsed group. TJA-II, ACA, WFA, and BPL showed stronger binding in the relapsed group. PNGase F treatment of TNBC cell lysates suggested that TJA-II and ACA bind O-glycans. TJA-II staining of tissue sections revealed strong binding to cell surface membranes and to the cytoplasm of TNBC cells, but not to other types of cells. Significantly more TNBC cells were stained in tissue sections from relapsed than non-relapsed patients. TNBC cells from relapsed patients showed a unique lectin reactivity, with higher levels of TJA-II (also WFA and BPL) binding than in non-relapsed patients. The results are potentially useful to develop new prognostic and therapeutic tools.

ESMO 2020: highlights in breast cancer.

Despite the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, results of several pertinent studies in the field of breast cancer (BC) were presented in a virtual format at the 2020 European Society of Medical Oncology (ESMO) Congress. Early results of the MonarchE trial investigating the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib to standard adjuvant endocrine therapy indicated a lower recurrence rate in the combination group in a high-risk population of patients with early stage hormone receptor (HR)-positive/HER2-negative BC. In contrast, the PALLAS study evaluating adjuvant palbociclib could not confirm these results. Subtle differences in the respective trial populations, a higher discontinuation rate in PALLAS, or substance-specific differences may be responsible. In HER2-positive early stage BC, long-term results of the ADAPT-TP trial support the notion that chemotherapy-free treatment may be possible in a subset of patients with favourable response to HER2-directed therapy without compromising long-term outcome. The phase III IMpassion031 trial evaluated the addition of atezolizumab to neoadjuvant anthracycline/taxane-containing chemotherapy in triple-negative BC (TNBC). A significant improvement in terms of pathologic complete remission rate was observed but data concerning long-term outcome must be awaited. Final overall survival (OS) analysis of IMpassion130 confirmed the clinically relevant OS improvement observed with the addition of atezolizumab to first-line nab-paclitaxel in metastatic PD-L1 positive TNBC. In contrast, no benefit was observed with the addition of atezolizumab to solvent-based paclitaxel in a similar population. This contradiction is commonly explained by the need for corticosteroid co-medication with conventional paclitaxel, but the exact reason remains poorly understood. Antibody–drug conjugates (ADCs) have been successfully established in HER2-positive breast cancer; in TNBC, the phase III ASCENT trial compared the ADC sacituzumab govitecan with chemotherapy by physician’s choice in pretreated metastatic patients. A significant improvement in terms of progression-free survival and OS was observed rendering this drug a potential novel standard in this patient population.

Effect of Celecoxib Added to Standard Adjuvant Therapy for Colon Cancer

Aspirin use may reduce the risk for developing colorectal cancer. After surgery and adjuvant therapy, aspirin may also reduce the risk for colorectal

Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer

Aspirin and cyclooxygenase 2 (COX-2) inhibitors have been associated with a reduced risk of colorectal polyps and cancer in observational and randomized studies. The effect of celecoxib, a COX-2 inhibitor, as treatment for nonmetastatic colon cancer is unknown. To determine if the addition of celecoxib to adjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) improves disease-free survival in patients with stage III colon cancer. Cancer and Leukemia Group B (Alliance)/Southwest Oncology Group 80702 was a 2 × 2 factorial design, phase 3 trial conducted at 654 community and academic centers throughout the United States and Canada. A total of 2526 patients with stage III colon cancer were enrolled between June 2010 and November 2015 and were followed up through August 10, 2020. Patients were randomized to receive adjuvant FOLFOX (every 2 weeks) for 3 vs 6 months with or without 3 years of celecoxib (400 mg orally daily; n = 1263) vs placebo (n = 1261). This report focuses on the results of the celecoxib randomization. The primary end point was disease-free survival, measured from the time of randomization until documented recurrence or death from any cause. Secondary end points included overall survival, adverse events, and cardiovascular-specific events. Of the 2526 patients who were randomized (mean [SD] age, 61.0 years [11 years]; 1134 women [44.9%]), 2524 were included in the primary analysis. Adherence with protocol treatment, defined as receiving celecoxib or placebo for more than 2.75 years or continuing treatment until recurrence, death, or unacceptable adverse events, was 70.8% for patients treated with celecoxib and 69.9% for patients treated with placebo. A total of 337 patients randomized to celecoxib and 363 to placebo experienced disease recurrence or died, and with 6 years' median follow-up, the 3-year disease-free survival was 76.3% for celecoxib-treated patients vs 73.4% for placebo-treated patients (hazard ratio [HR] for disease recurrence or death, 0.89; 95% CI, 0.76-1.03; P = .12). The effect of celecoxib treatment on disease-free survival did not vary significantly according to assigned duration of adjuvant chemotherapy (P for interaction = .61). Five-year overall survival was 84.3% for celecoxib vs 81.6% for placebo (HR for death, 0.86; 95% CI, 0.72-1.04; P = .13). Hypertension (any grade) occurred while treated with FOLFOX in 14.6% of patients in the celecoxib group vs 10.9% of patients in the placebo group, and a grade 2 or higher increase in creatinine levels occurred after completion of FOLFOX in 1.7% vs 0.5% of patients, respectively. Among patients with stage III colon cancer, the addition of celecoxib for 3 years, compared with placebo, to standard adjuvant chemotherapy did not significantly improve disease-free survival. ClinicalTrials.gov Identifier: NCT01150045.

Regulation of Long Non-Coding RNAs by Plant Secondary Metabolites: A Novel Anticancer Therapeutic Approach.

Simple SummaryCancer is caused by the rapid and uncontrolled growth of cells that eventually lead to tumor formation. Genetic and epigenetic alterations are among the most critical factors in the onset of carcinoma. Phytochemicals are a group of natural compounds that play an essential role in cancer prevention and treatment. Long non-coding RNAs (lncRNAs) are potential therapeutic targets of bioactive phytochemicals, and these compounds could regulate the expression of lncRNAs directly and indirectly. Here, we critically evaluate in vitro and in vivo anticancer effects of phytochemicals in numerous human cancers via regulation of lncRNA expression and their downstream target genes.Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play an essential role in various cellular activities, such as differentiation, proliferation, and apoptosis. Dysregulation of lncRNAs serves a fundamental role in the progression and initiation of various diseases, including cancer. Precision medicine is a suitable and optimal treatment method for cancer so that based on each patient’s genetic content, a specific treatment or drug is prescribed. The rapid advancement of science and technology in recent years has led to many successes in this particular treatment. Phytochemicals are a group of natural compounds extracted from fruits, vegetables, and plants. Through the downregulation of oncogenic lncRNAs or upregulation of tumor suppressor lncRNAs, these bioactive compounds can inhibit metastasis, proliferation, invasion, migration, and cancer cells. These natural products can be a novel and alternative strategy for cancer treatment and improve tumor cells’ sensitivity to standard adjuvant therapies. This review will discuss the antineoplastic effects of bioactive plant secondary metabolites (phytochemicals) via regulation of expression of lncRNAs in various human cancers and their potential for the treatment and prevention of human cancers.

The Effect of Previous Irradiation for Patients With Prosthetic Breast Reconstruction: A Meta-Analysis.

Results regarding immediate prosthetic breast reconstruction after postmastectomy radiation therapy (PMRT) have been inconsistent. The authors aimed to assess the efficacy and safety of PMRT before immediate prosthetic breast reconstruction for patients with breast cancer. Electronic databases (PubMed, EmBase, and the Cochrane Library) were systematically searched to identify eligible studies from their inception until March 2020. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was applied as an effect estimate and calculated using the random-effects model. Nineteen studies including a total of 6757 patients were selected for final meta-analysis. The pooled OR showed that PMRT was associated with a higher incidence of reconstruction failure (OR = 2.57; 95% CI =1.55-4.26; P < 0.001), capsular contracture (OR = 5.99; 95% CI = 3.12-11.47; P < 0.001), and overall complications (OR = 2.52; 95% CI = 1.68-3.79; P < 0.001). It was also associated with a lower incidence of patient satisfaction (OR = 0.29; 95% CI = 0.16-0.52; P < 0.001) and good aesthetic results (OR = 0.25; 95% CI = 0.12-0.52; P < 0.001) compared with those who did not undergo PMRT. These significant associations could be affected by study design, mean age, stage of immediate breast reconstruction, follow-up, and study quality. Although PMRT is the standard adjuvant therapy for mastectomy patients treated with immediate implant-based breast reconstruction, PMRT for patients undergoing immediate implant-based breast reconstruction has been associated with high risks of reconstruction failure, capsular contracture, and overall complications as well as low incidences of patient satisfaction and good aesthetic results.

Abstract OT-01-02: Adaptlate -a randomized, controlled, open-label, phase-iii trial on adjuvant dynamic marker - adjusted personalized therapy comparing abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy in (clinical or genomic) high risk, hr+/her2- early breast cancer

Abstract Goals: The WSG ADAPT trial program is one of the first new generation trials addressing the issue of individualization of (neo)-adjuvant decision-making in early breast cancer (EBC) in a subtype-specific manner. The first WSG ADAPT umbrella trial (NCT01779206) aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment and to omit chemotherapy in a large cohort of early high risk HR+/HER2- patients. The aim of the ADAPTlate phase-III-trial is to improve adjuvant therapy for patients at high risk for late disease recurrence, who have completed definite locoregional therapy (with or without neoadjuvant or adjuvant chemotherapy) and are under adjuvant endocrine treatment. This high-risk population does not derive optimal benefit from standard ET, often develops secondary resistance against ET and consequently late recurrences. With ADAPTlate, it is planned to evaluate whether patients with high-risk EBC derive additional benefit from adding abemaciclib to ET even 2-6 year after their initial diagnosis. Abemaciclib has been shown to improve outcome in metastatic breast cancer and recently, even in early breast cancer when given as part of primary therapy. Methods: WSG-ADAPTcycle is a prospective, multi-center, interventional, two-arm, non-blinded, randomized, controlled adjuvant phase III trial (NCT not yet assigned). It investigates whether patients with HR+/HER2- EBC identified as high-risk during screening (based on clinical or genomic risk) derive additional benefit from 2 years of the CDK4/6 inhibitor abemaciclib combined with ET compared to ET alone. Starting Q3 2020 (enrollment 36 months, 50 sites), 1250 patients will be screened and 903 randomized in a ratio 3:2 (602 to abemaciclib + ET; 301 to standard ET). Pre-/postmenopausal patients with histologically confirmed invasive HR+/HER2- EBC and 2-6 years after primary diagnosis, with either known high clinical risk (c/pN 2-3 OR high CTS score in pN 0-1 OR non-pCR after neoadjuvant chemotherapy in cN 1 or G3 tumors OR G3 and Ki-67 ≥ 40% in pN 0-1) or known high genomic risk (Oncotype Dx® / RS &amp;gt;25 in c/pN 0, RS &amp;gt;18 in c/pN 1 OR high risk Prosigna®, EPclin® or Mammaprint® in pN 0-1) or intermediate clinical, but unknown genomic risk (luminal B-like (G3 or Ki-67 ≥20%) in c/pN 0-1 AND Oncotype DX® in screening either RS &amp;gt;25 in c/pN 0 or RS &amp;gt;18 in c/p N1) will be eligible. Treatment duration is 2 years for the interventional abemaciclib + ET (premenopausal: AI+GnRH) arm, followed by at least 3-6 years ET alone. Patients in control arm will receive 5-8-years ET at investigator´s choice. ePROs are collected using CANKADO. Primary objective is to demonstrate superiority of invasive disease-free survival (iDFS) of abemaciclib + ET vs. standard ET. Secondary objectives include overall survival (OS), distant disease-free survival (dDFS), occurrence of CNS metastases, quality of life (EORTC QLQ-C30, QLQ-BR23, EQ-5D-5L) and translational research. Translational analyses: Exploratory tissue biomarker research will be conducted to assess alterations in molecular markers (e.g., ESR1, PIK3CA, CCND1, CDKN2A, RB1). In addition, ctDNA/ctRNA from optional blood samples will be assessed for mutations and gene expression relevant for HR+/HER2- EBC using the most appropriate technology at the time of testing. Conclusions: ADAPTlate seeks to evaluate whether enhancing ET with a CDK 4/6 inhibitor is superior to ET alone in patients with clinical or genomic high risk EBC even 2-6 years after their initial diagnosis. Translational research aims at assessing potential mechanisms of resistance to endocrine and/or CDK4/6 targeted therapy. Citation Format: Oleg Gluz, Tom Degenhardt, Norbert Marschner, Matthias Christgen, Hans Heinrich Kreipe, Ulrike Nitz, Ronald Kates, Timo Schinkoethe, Monika Graeser, Rachel Würstlein, Sherko Kuemmel, Nadia Harbeck, West German Study Group. Adaptlate -a randomized, controlled, open-label, phase-iii trial on adjuvant dynamic marker - adjusted personalized therapy comparing abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy in (clinical or genomic) high risk, hr+/her2- early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-01-02.

Abstract GS3-00: First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) &amp;lt; 25: SWOG S1007 (RxPonder)

Abstract Funding: Supported by National Cancer Institute grants U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180868, U10CA180863; and in part by Susan G. Komen for the Cure® Research Program, The Hope Foundation for Cancer Research, Breast Cancer Research Foundation, and Genomic Health, Inc. Acknowledgement: The authors wish to thank Dr. Ana M. Gonzalez-Angulo, MD, for her invaluable contributions to the design and implementation of this study. Background: The clinical utility of the RS to determine CT benefit is well established in pts with HR+, HER2-, axillary lymph node (LN)-negative BC. Retrospective analyses from SWOG S8814 support the potential prognostic and predictive role of RS for CT benefit in postmenopausal pts with LN+ BC. SWOG S1007 is a prospective, randomized trial of endocrine therapy (ET) vs. chemoendocrine therapy (CET) in women with 1-3 +LN and a RS &amp;lt; 25 (NCT01272037). Methods: Eligibility criteria included women &amp;gt; 18 years of age with HR+, HER2- BC and 1-3 +LN and no contraindications to taxane and/or anthracycline based CT. Women with a RS &amp;lt; 25 were randomized to receive ET or CET in 1:1 randomization using 3 stratification factors: (1) RS (0-13 vs.14-25); (2) menopausal status; and (3) axillary nodal dissection vs. sentinel node biopsy. The primary objective was to determine the effect of CT on invasive disease-free survival (IDFS) and whether the effect depended on the RS. The primary analysis was to test for a significant interaction of the treatment arm and continuous RS using a Cox regression model for IDFS, adjusting for treatment, RS, and menopausal status. A total of 832 IDFS events were expected for the final analysis. Secondary objectives included overall survival (OS). The protocol specified that interaction between treatment and the stratification variables was to be tested and, if significant, separate analyses performed by stratum. Annual interim analyses were planned starting at 24% of events. At the third interim analysis with 410 IDFS events, the Data and Safety Monitoring Committee recommended reporting results, with a decision by the NCI’s Cancer Therapy Evaluation Program, the study sponsor. Results: Of the 9,383 women screened from 2/28/11-9/29/17, 5,083 pts (54.2%) were randomized. With a median follow-up of 5.1 years, 447 IDFS events have been observed. For the primary analysis, the interaction test for CT benefit and continuous RS was not statistically significant, p=0.30. In a model with CT, RS, and menopausal status (no interaction term), higher continuous RS was associated with worse IDFS [HR 1.06, 2-sided p&amp;lt;0.001, 95% Confidence Interval (CI) 1.04-1.07], and CT was associated with an improvement in IDFS (HR 0.81, p=0.026, 95% CI 0.67-0.98). In a pre-specified analysis, a significant interaction was identified between CT and menopausal status (p=0.004), necessitating separate analyses by menopausal status. In postmenopausal pts (N=3350, 67%), adjusting for continuous RS, the HR for CET vs. ET was not significant (HR=0.97, p=0.82, 95% CI 0.78-1.22; 5-year IDFS 91.6% vs. 91.9%) indicating no benefit from CT. In premenopausal pts (N=1665, 33%), the HR (0.54) was statistically significant (p=0.0004, 95% CI 0.38-0.76; 5-year IDFS 94.2% vs. 89.0%), indicating CT benefit. In premenopausal pts, ovarian suppression was performed in 15.9% vs. 3.7% (ET vs. CET), and 47.9% vs. 26.4% reported menstruation after 6 months of treatment. Although the number of events is limited, the HR for treatment adjusted by RS for OS in premenopausal pts was 0.47 (p=0.032, 95% CI 0.24-0.94). At this time, there is no differential effect with CT in regard to other stratification factors. Conclusions: There is a significant differential treatment effect of CT benefit based on RS for premenopausal vs. postmenopausal women requiring separate analyses. While only 54% of the protocol specified events are recorded and pts will be followed for 15 years, the current data show that adjuvant therapy can be de-escalated to ET alone in postmenopausal pts with a RS &amp;lt; 25 and 1-3 +LN. However, there is a strong IDFS benefit for CET in premenopausal pts, with an early indication of an OS improvement. Citation Format: Kevin Kalinsky, William E Barlow, Funda Meric-Bernstam, Julie R Gralow, Kathy S Albain, Daniel Hayes, Nancy Lin, Edith A Perez, Lori J Goldstein, Stephen Chia, Subkhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Miguel Martín, Miguel Gil Gil, Claudia Arce-Salinas, Etienne Brain, In Hae Park, Jean-Yves Pierga, Ana Hernandez Lluch, Manuel Ramos Vasquez, Manuel Ruiz Borrego, Kyung Hae Jung, Jean-Marc Ferrero, Anne Schott, Steve Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Debu Tripathy, Gabriel Hortobagyi, Lajos Pusztai. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) &amp;lt; 25: SWOG S1007 (RxPonder) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-00.

Abstract PS11-30: Can metronomic maintenance therapy (MMT) after completion of standard therapy help prevent relapses in patients (Pts) with non-metastatic triple-negative breast cancer (TNBC)

Abstract Background: In-spite of the standard neoadjuvant and adjuvant therapies, stage for stage many more patients with TNBC relapse. This may be because of lack of effective maintenance therapy for TNBC Pts. Recently MMT is being explored to improve outcomes in TNBC. We present a retrospective and prospective analysis of consecutive Pts with TNBC treated at BKLWalawalkarHospital, the rural outreach center of Tata Memorial Centre (India), wherein the outcome of TNBC Pts receiving MMT is being compared to historical control group who did not receive the same. Methods: After standard anthracycline or anthracycline+taxane based therapy, TNBC Pts were either observed (Sept 2003 to March 2011) or received MMT (Nov 2008 to Dec 2018).MMT consisted of 2 phases: initial 12 weeks of daily oral celecoxib (200 mg BD) and cyclophosphamide (50 mg OD) along with 12 doses of weekly IV cisplatin (25 mg/m2). This was followed by 1 year of Phase II maintenance consisting of oral daily metformin (500 mg BD), cyclophosphamide (50 mg OD) along with weekly methotrexate (12 mg/m2).When CAF is the standard regimen 2 phases of maintenance was given , after anthracyclines and taxanes were proved as a standard regimen maintenance was restricted to Phase II considering overlapping toxicities like neuropathy. Results: There were 118 evaluable TNBC Pts. 25 Pts did not receive any MMT.Of the 93 remaining Pts initial 25 received both Phase I &amp; II MMT , 1 patient received only phase I and subsequent 61 Pts have received only Phase II MMT. 6 patients progressed while on initial standard therapy and were not evaluable to assess the effect of MMT .Hence 112 patients are analysed further for outcome.STAGE STRATIFICATION : 8 Pts(6.7%) had AJCC Stage I; 48 Pts(40.6%) had AJCC Stage II; &amp; 62 patients(52.5) had AJCC Stage III disease.MMT and observation groups were comparable with respect to baseline characteristics such as age &amp; stage . Out of 112 patients 87 received MMT and 9 events were noted ,25 did not received MMT and 12 events were noted.EFS by March 2020 is 89.7% in MMT group and 52% in non- MMT group . Median EFS in MMT group is 11.3 yrs ( 9.4 yrs-13.14 yrs 95% CI) , in Off MMT group median EFS 9.2 yrs( 6.4-12 yrs 95% CI).Overall comparison was done by Log rank analysis (Significance 0.006).Median overall survival in OMCT group is 11.8yrs ( 9.9yrs-13.8yrs 95% CI), in non MMT group OS is 9.8yrs( 7.1 yrs-12.6yrs) with significance 0.002.61 patients who received Phase II MMT OS is 13.4 yrs ( 12.5yrs-14.4 yrs 95% CI).By stage stratification in non MMT group 2 patients belong to Stage I , 9patients belongs to Stage II and 14 patients belongs to Stage III. TOXICITIES : MTX 25% dose reduction was done in 7 patients due to Grd2 Mucositis, cyclophosphamide alone was stopped in 1 patient due to grade 3 fatigue, MTX and Cyclophosphamide was stopped in 2 patientsdue grade3 anemia and grade 4 neutropenia, blood transfusion was done in them.Toxicities are much less when compared to CREATEX trial and the follow up duration is very long. Conclusion: Most of the TNBC patients relapse in the early period of follow up and there is an unmet need in the improvement of management. If low dose chemotherapy is given for 1 yr there is a significant improvement in EFS and OS without muchdecrease in QOL.l. This strategy is worthy of being evaluated in definitive randomized trials in TNBC women with large numbers. Citation Format: Kripa Bajaj, Shripad Banavali. Can metronomic maintenance therapy (MMT) after completion of standard therapy help prevent relapses in patients (Pts) with non-metastatic triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-30.

Abstract PS2-07: Outcomes associated with disseminated tumor cells at surgery after neoadjuvant chemotherapy in high-risk early stage breast cancer: The I-SPY SURMOUNT study

Abstract Background: Disseminated tumor cells (DTCs) in bone marrow detected after treatment may represent occult residual disease. We enumerated DTCs after neoadjuvant chemotherapy (NACT) in patients (pts) diagnosed with high-risk early stage breast cancer and examined the relationship of these cells with response and survival. Methods: I-SPY SURMOUNT is a sub-study of the I-SPY 2 TRIAL (NCT01042379). Pts enrolled on I-SPY 2, who signed consent for this sub-study, had bone marrow aspirates (BMA) collected after NACT at the time of surgery. DTCs were isolated and enumerated from BMA using immunomagnetic enrichment/flow cytometry (IE/FC). DTCs were defined as EPCAM-positive and CD45-negative nucleated cells. Samples were considered positive using a predetermined threshold of &amp;gt;4 DTCs per mL (Magbanua et al, unpublished data). Pathologic response was assessed using the residual cancer burden (RCB) method at local sites, and pts underwent standard adjuvant therapy if indicated and follow up for recurrence events and death. Relationship of DTCs with clinicopathologic variables was examined using Chi-squared test. Group means were compared using t tests. The log-rank test was used to compare survival curves. Results: A total of 73 patients were enrolled, 51 of whom had successful DTC assessment. The median DTC per mL was 4 (interquartile range 1.2-11.6). 24/51 (47%) were DTC-positive. Clinical characteristics by DTC status are shown in the table. DTC-positive pts were significantly younger (p=0.02) and had larger pretreatment tumors (longest diameter by magnetic resonance imaging) compared to DTC-negative pts (p=0.032). DTCs were not associated with receptor subtype. Thirty pts (41%) achieved a pathologic complete response (pCR). DTCs were not associated with pCR (p= 0.166); however, DTC-positive patients were significantly more likely to have residual cancer (RCB-II/III) after NACT compared to DTC-negative patients (OR 3.3, p=0.037). Median follow up of this cohort was 2.8 years (range: 0.9-4.8). Interim survival analysis showed that DTCs were not significantly correlated with EFS (p=0.6) or DRFS (p=0.41). Conclusions: Detection of DTCs at surgery after NACT is significantly more common in young patients, those with larger tumors, and those with residual disease at surgery. While these associations suggest higher risk for later recurrence, larger studies and longer follow up are necessary to determine if DTCs add prognostic value over pathologic evaluation alone for pts receiving NACT. Citation Format: Mark Jesus M Magbanua, Laura van 't Veer, Amy Clark, A. Jo Chien, Judy Boughey, Heather Han, Anne Wallace, Heather Beckwith, Minetta Liu, Christina Yau, E. Paul Wileyto, Lamorna Brown Swigart, Jane Perlmutter, Lauren Bayne, Shannon Deluca, Stephanie Yee, Erica Carpenter, Laura Esserman, John Park, Lewis Chodosh, Angela DeMichele. Outcomes associated with disseminated tumor cells at surgery after neoadjuvant chemotherapy in high-risk early stage breast cancer: The I-SPY SURMOUNT study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-07.

Comparison of survival outcomes between laparoscopic surgery and abdominal surgery for radical hysterectomy as primary treatment in patients with stage IB2/IIA2 cervical cancer.

To investigate the long-term oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for the treatment of stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy. We conducted a multicenter, retrospective, case-matching study. The differences in overall survival (OS) and disease-free survival (DFS) between the LRH and ARH were compared under the conditions of real-world study and case-control matching (1:1 matching). There was no significant difference in the outcomes of LRH (n = 580) and ARH (n = 1653) in 5-year OS and DFS (OS: 80.6% vs. 86.1%, p = 0.421; DFS: 78.6% vs. 80.7%, p = 0.376). After 1:1 matching, there was no difference in 5-year OS and DFS between LRH (n = 554) and ARH (n = 554) (OS: 80.4% vs. 84.5%, p = 0.993; DFS: 79.0% vs. 78.8%, p = 0.695). Before and after matching, the surgical approach was not an independent risk factor for 5-year OS and DFS, and postoperative adjuvant therapy affected patient prognosis. Further subgroup analysis suggested that there was no difference in LRH (n = 313) and ARH (n = 1092) in 5-year OS or DFS in patients who underwent standard postoperative adjuvant therapy (OS: 83.0% vs. 87.7%, p = 0.992; DFS: 79.0% vs. 82.5%, p = 0.323). After 1:1 pairing, the 5-year OS and DFS in LRH (n = 295) and ARH (n = 295) showed no difference. Before and after matching, the surgical approach was not an independent risk factor affecting the 5-year OS and DFS. There was no difference in the oncological outcomes between laparoscopic and abdominal surgery in patients with stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy. The ethical approval number is NFEC-2017-135, and the clinical research registration number is CHiCTR1800017778 (International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/).

Anti-PD-1 antibody SHR-1210 combined with apatinib as adjuvant treatment in patients with hepatocellular carcinoma at high risk of recurrence after radical resection: Preliminary results from a multicenter, randomized, controlled phase II trial.

285 Background: There is no globally recognized standard adjuvant therapy for HCC after radical resection. Herein, we explored to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210 combined with apatinib as adjuvant treatment versus hepatic arterial infusion (HAI) in HCC patients with high risk of recurrence after radical resection. Methods: This was an ongoing multicencer, randomized, controlled phase 2 trial. All HCC patients were Child-Pugh Class A, and confirmed as high risk of recurrence such as portal vein tumor thrombus (PVTT) involved in second-order branch or above, microvascular invasion (MVI) and microsatellite leisions. Eligible patients were randomly assigned (1:1) to receive SHR-1210 (200mg, q2w) and apatinib (250mg, q.d.) for 12 cycles, or two times of standard HAI treatments (epirubicin 80-100mg or epirubicin 50mg+oxaliplatin 50mg). The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included safety and quality of life score (QoL). Results: From Jun 12, 2019 to Sep 15, 2020, 32 Chinese HCC patients (pts) (16pts in SHR-1210-apatinib group and HAI group, respectively) had been recruited. Full analysis (FAS) population contained 29 pts and intention to treat (ITT) population included 32 pts. The hadzard ratio for relapse or death with SHR-1210-apatinib as compared with HAI was 0.48 (95% CI 0.12-1.75; P = 0.2992) and 0.38 (95% CI 0.11-1.20; P = 0.0910) in FAS and ITT population, respectively, at date cutoff. Median RFS was not reached and 10.5 months in SHR-1210-apatinib group and HAI group, respectively. The average QoL score during treatment was 48.8 and 49.2 in SHR-1210-apatinib group and HAI group, respectively. The most common grade 3 or 4 adverse events occurred in SHR-1210-Apatinib were γ-glutamyltransferase (GGT) increase (18.75%), leukopenia (12.50%), neutrophil count decrease, alanine and aspartate aminotransferase increase (12.50%), while in HAI group were lymphocyte count decrease (7.69%), hemoglobin increase (7.69%) and GGT increase (7.69%). Conclusions: In HCC patients with high risk of recurrence after radical resection, SHR-1210 combined with apatinib was tolerable, and might offer a new promising choice superior to HAI for adjuvant therapy in HCC, further study is needed to reach the pre-defined primary endpoint. Clinical trial information: NCT03839550.

The role of lymphadenectomy in patients with stage III&IV uterine serous carcinoma: Results of multicentric Turkish study

ObjectiveThe aim of this study was to evaluate clinicopathological features, oncological outcome and prognostic factors for recurrence in advanced stage uterine serous carcinoma (USC) patients. MethodsPatients with 2009 International Federation of Gynecology and Obstetrics stage III&IV uterine serous carcinoma were enrolled from 4 gynecologic oncology centers and a study group was created. Response to therapy was evaluated according to the WHO criteria. Progression-free survival (PFS) and overall survival (OS) estimates were determinated by using the Kaplan-Meier method. Survival curves were compared with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. ResultsEntire cohort included 63 patients. Median age of cohort was 64 years. Thirty-five (55.6 %) patients were stage IV. Lymphadenectomy was performed in 57 (90.5 %) patients and lymph node metastasis was positive in 45 (71.4 %) patients. Maximal cytoreduction (no residue tumor) was achieved in 53 (84.1 %) patients. However, optimal cytoreduction (residue tumor ≤1 cm) was achieved in 6 (9.5 %) patients and suboptimal cytoreduction (residue tumor >1 cm) was achieved in 3 (4.8 %) patients. Median follow-up time was 19 (range;1–152) months. Complete clinical response was obtained in 58 (92.1 %) patients after standard adjuvant therapy. Disease failure was detected in 25 patients. Study group had a 2-year PFS of 51 % and 2-year OS of 80 %. On multivariate analysis, performing lymphadenectomy was an independent prognostic factor for PFS (Odds ratio: 24.794, 95 % Confidence Interval: 4.214−145.869; p < 0.001). ConclusionLymphadenectomy should be a part of the standard surgical therapy in advanced stage USC.

Male breast carcinoma in the oldest old: an extremely rare entity

Male breast cancer is a rare disease and is seen in &lt;1% of all newly diagnosed cancers in men. The present understanding of its biology, natural history, and treatment strategies is mainly based on the research findings on female breast cancer. The median age of diagnosis is 67 years. Very few cases of male breast cancer have been reported in men aged more than 70 years of age, however no case has been reported in age &gt;85-year-old (age group now referred to as the oldest old). Risk factors include increasing age, radiation exposure, hormonal imbalance including testicular dysfunction, infertility, obesity, cirrhosis and genetic predisposition. Survival in men with breast cancer is similar to survival in women with breast cancer matched for age and stage. However, men have poor prognosis because of the more advanced stage of their cancer at the time of diagnosis. The surgical operation is usually mastectomy with axillary clearance or sentinel node biopsy. Indications for radiotherapy are similar to that for female breast cancer. Because 90% of the patients are oestrogen receptor-positive, tamoxifen is a standard adjuvant therapy, but some individuals could also benefit from chemotherapy. We report a case of male breast cancer in an 88-year-old man which is probably first in in the literature to the best of our knowledge and a brief summary of its natural history and treatment strategies are given.