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  • American Association for Cancer Research (AACR)  (8)
  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. OT-23-02-OT-23-02
    Abstract: Background: Proper patient selection is crucial to maximize aestethic outcome in breast reconstructive surgery. No specific patients selection criteria have been developed to choose between prepectoral versus subpectoral implant-based reconstruction. A quantitative tool able to determine the pectoralis muscle individual characteristics might be helpful to discriminate a priori the patients who will experience better aesthetic outcome and less complications following a pre-pectoral versus a sub-pectoral approach. Preoperative pectoralis muscle assessment may optimize patients’ selection for the breast reconstructive technique. Trial design: This is a multicentric trial in which, patients candidated to risk reducing mastectomy fulfilling inclusion criteria, will undergo a preoperative MRI prior to randomization to pre-pectoral versus sub-pectoral implant placement in immediate breast reconstruction. Volumetric analysis of the pectoralis major muscle (cm2) and measurement of the subcutaneous adipose tissue in the breast region, will be performed to assess anatomic characteristics of the pectoralis muscle using a sagittal T1 fat suppressed sequence. The volume of the pectoralis muscle will be calculated by measuring differences in density with the MRI. In all patients, the pectoralis muscle area on the left and right side will be determined separately and the two values will be averaged. The volumetric assessment will be performed by two expert radiologists. BREAST-Q© questionnaire will be completed by each patient prior to surgery and at the follow up evaluations. Breast reconstruction will be performed immediately after nipple-sparing mastectomy (Arm 1: breast implant placed above the pectoralis major muscle (pre-pectoral); Arm 2: breast implant placed below the pectoralis major muscle (sub-pectoral)). Number of revisional surgeries, explantations, infections, seromas, flap necrosis, will be compared between two groups and correlated with MRI pectoralis muscle volume. Post-operative follow-up evaluations at 6 and 12-months to assess capsular contracture and BREAST-Q changes will be performed. Eligibility criteria: Inclusion criteria: •Female patient•Ages 18-60•Patients undergoing risk reducing mastectomy with immediate implant-based reconstruction •Signed informed consent Exclusion Criteria: •Prior chest wall irradiation •Patients with a contraindication to immediate breast reconstruction.•Patients with history of smoking, •BMI & gt; 40, •D cup breast size•grade III ptosis Aims: To identify variables measured at preoperative MRI pectoralis muscle’s volumetric analysis that correlate with aesthetic outcome and complication rate in pre-pectoral versus sub-pectoral implant based reconstruction. Statistical methods: The assumption of distributional normality will be tested using the Shapiro-Wilk test. Comparisons of two variables will be carried out using the Wilcoxon test for paired groups and the Mann-Whitney test for unpaired groups. Present accrual and target accrual: The trial has been submitted for IRB approval at the ethical commission of Italian Switzerland. Recruitment has not started yet. With an enrollment ratio of 1:1, fifty patients (25 per arm) need to be recruited to ensure a power of 80% with a two sides alpha error of 0.05. Contact information: marialuisa.gasparri@eoc.ch Citation Format: Maria Luisa Gasparri, Thorsten Kuehn, Isabel Rubio, Philip Poortmans, Diana Lueftner, Orit Kaidar-Pearson, Beat Thuerlimann, Yves Harder, Daniel Schmauss, Francesco Meani, Claudia Rauh, Michael David Mueller, Malgorzata Banys-Paluchowski, Andrea Papadia, Valerio Vitale, Stefania Rizzo, Oreste Davide Gentilini. Volumetric analysis of the pectoralis major muscle as preoperative tool to select patients undergoing pre-pectoral versus sub-pectoral implant based breast reconstruction after risk reducing mastectomy [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-23-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 2
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 5, No. 11_Supplement ( 2012-11-01), p. SS-01-SS-01
    Abstract: Background: Metformin has been associated with a significant reduction in cancer incidence and mortality in diabetic patients relative to other antidiabetic drugs, including positive results specifically in breast cancer. In a recent window-of-opportunity trial in 200 non-diabetic women with breast cancer, we showed a heterogeneous effect of metformin on breast cancer proliferation (Ki-67 labeling index) depending on insulin resistance, with a trend to a decreased proliferation in women with insulin resistance (HOMA & gt;2.8) and an opposite trend in women with normal insulin sensitivity (Bonanni et al. JCO 30:2593, 2012). Here we performed an exploratory study to determine whether metformin has antiproliferative effects on adjacent lobular or ductal intraepithelial neoplasia (LIN or DIN) and on distant ductal hyperplasia and whether these effects are different according to specific host and tumor characteristics. Previous studies showed that Ki-67 LI in atypical lesions predicts subsequent breast cancer risk. Methods: Baseline core biopsies of tumor tissue and blood samples were obtained at study entry and before surgery for pre/post-treatment comparisons. Patients were randomly assigned to metformin, 850 mg or placebo once daily on day 1-3 followed by two 850 mg tablets from day 4 to 28. At the time of surgical removal of the tumor, three to five specimens of adjacent (≥1 cm from the tumor) and distant ( & gt;1 cm from the tumor) grossly normal tissue (i.e., the surgical margins of quadrantectomy or lumpectomy, or the grossly free quadrants from mastectomy specimens) were obtained to assess systematically the prevalence of LIN or DIN and ductal hyperplasia. Results: Overall, the prevalence of LIN, DIN and ductal hyperplasia was 4.5% (9/200), 66.5% (133/200) and 35% (69/200), respectively. The Ki-67 LI was positively associated with DIN grade (p-trend & lt;0.001). The median (and IQ range) Ki-67 LI distribution of LIN+DIN was 12% (8-20) and 10% (6-22) on metformin and placebo, respectively (p=0.6), nor was there a significant difference of Ki-67 LI in any subgroup between treatment arms. However, compared with placebo, metformin exhibited different effects on Ki-67 according to DIN grade (delta=+4.4% in DIN1 vs -27.9% in DIN3, p-interaction=0.09), cancer HER2 status (median 12% vs. 10% in HER2-ve and 28% vs. 35% in HER2+ve, p-interaction=0.03), abdominal circumference (p=0.08), and BMI (p=0.17). Conclusions: Our findings illustrate the notion that the window of opportunity pre-surgical model provides insight into a drug's preventive potential by targeting tumor adjacent dysplastic (or intraepithelial neoplastic) cells and distant ductal hyperplastic cells. The model unravels the existence of the field cancerization effect in apparently normal breast tissue. Similar to our results on breast cancer tissue, metformin had no overall significant effect on breast preneoplasia proliferation but exhibited heterogeneous effects depending upon specific host and preneoplasia characteristics. Further studies are necessary to better understand the clinical implications of these findings. (Supported by the Italian Association for Cancer Research and Italian Ministry of Health 2009-RF-1532226). Citation Format: Andrea DeCensi, Valentina Aristarco, Matteo Lazzeroni, Clara Varricchio, Bernardo Bonanni, Matteo Puntoni, Giancarlo Pruneri, Massimiliano Cazzaniga, Andrea Vingiani, Davide Serrano, Aliana Guerrieri-Gonzaga, Oreste Gentilini, Harriet Johansson. Metformin effects on breast preneoplasia. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr SS-01.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 3
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 8, No. 10 ( 2015-10-01), p. 888-894
    Abstract: Metformin is associated with lower breast cancer risk in epidemiologic studies and showed decreased proliferation in HER2-positive breast cancer in a presurgical trial. To provide insight into its preventive potential, we measured proliferation by Ki-67 labeling index (LI) of intraepithelial lesions surrounding breast cancer. We randomly assigned 200 nondiabetic patients diagnosed with invasive breast cancer in core biopsies to metformin, 1,700 mg or placebo once daily for 28 days before surgery. Upon surgery, five to seven specimens of cancer adjacent (≤1 cm) and distant ( & gt;1 cm) tissue were screened for LCIS, ductal carcinoma in situ (DCIS), and ductal hyperplasia (DH). The prevalence of LCIS, DCIS, and DH was 4.5% (9/200), 67% (133/200), and 35% (69/200), respectively. Overall, metformin did not affect Ki-67 LI in premalignant disorders. The median posttreatment Ki-67 LI (IQR) in the metformin and placebo arm was, respectively, 15% (5–15) versus 5% (4–6) in LCIS (P = 0.1), 12% (8–20) versus 10% (7–24) in DCIS (P = 0.9), and 3% (1–4) versus 3% (1–4) in DH (P = 0.5). However, posttreatment Ki-67 in HER2-positive DCIS lesions was significantly lower in women randomized to metformin especially when ER was coexpressed: 22% (11–32) versus 35% (30–40) in HER2-positive DCIS (n = 22, P = .06); 12% (7–18) versus 32% (27–42) in ER-positive/HER2-positive DCIS (n = 15, P = .004). Eight of 22 (36%) HER2-positive DCIS were adjacent to HER2-negative invasive breast cancer. In tissue samples obtained following 4 weeks of study drug, proliferation was lower in HER2-positive DCIS for women randomized to metformin versus placebo. An adjuvant trial incorporating metformin in HER2-positive DCIS is warranted. Cancer Prev Res; 8(10); 888–94. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. P5-12-02-P5-12-02
    Abstract: Background: In a presurgical trial in 200 non-diabetic women with breast cancer, we previously showed a heterogeneous effect of metformin on the Ki67, with a decreased proliferation in women with insulin resistance (HOMA & gt;2.8) and an opposite effect in women with HOMA≤ 2.8 (Bonanni et al. JCO 30:2593, 2012). Here we determined the effect of metformin on noninvasive proliferative disorders. Methods: Patients with operable breast cancer were randomly assigned to metformin, 850 mg or placebo once daily on days 1-3 followed by two 850 mg tablets after dinner on days 4 to 28. A total of 3-5 specimens of adjacent (≤1 cm from tumor) and distant ( & gt;1 cm from tumor) tissue were obtained from the surgical specimens to assess systematically the prevalence of LCIS and DCIS adjacent to invasive cancer and of distant ductal hyperplasia (DH) in normal tissue. We also determined the effect of metformin on Ki67 in these lesions overall and by molecular subtype. All HER2 2+ DCIS by IHC were assessed by FISH. Results: Overall, the prevalence of LCIS, DCIS and DH was 4.5% (9/200), 66% (132/200) and 35% (69/200), respectively. The Ki67 was positively associated with DCIS grade (p-trend & lt;.001). The median levels of Ki67 by treatment arm in different premalignant groups is summarized below Median (IQR) Ki67 level (%) in premalignant disorders by treatment armPremalignant groupPremalignant subgroupMetformin armPlacebo armp-value*p-interaction‡LCIS (n=9) 15 (5-15)5 (4-6)0.1 DH (n=69) 3 (1-4)3 (1-4)0.5 All DCIS (n=132) 12 (8-20)10 (7-24)0.9  DCIS grade 1/2 (n=108)10 (7-16)10 (6-17)0.90.2 DCIS grade 3 (n=24)33 (25-55)40 (32-40)0.2  HER2+ve (n=22)22 (11-32)35 (30-40)0.060.04 HER2-ve (n=58)16 (10-20)17 (8-26)0.7  ER+ve/HER2+ve (n=15)12 (7-18)32 (27-42)0.0040.001 ER+ve/HER2-ve (n=53)16 (10-20)15 (8-22)0.8  PR+ve/HER2+ve (n=12)18 (12-18)32 (24-44)0.020.05 PR+ve/HER2-ve (n=48)16 (10-20)12 (8-20)0.6 *Wilcoxon rank-sum test; ‡ p-interaction between treatment and DCIS grade or HER2 status from a linear regression model, adjusted for age and BMI. The effect of metformin on DCIS was different by HER2 status (p-interaction=.04) and, among this molecular subtype, by ER and PR status (p-interaction=.001 and .02, respectively). In HER2+ve DCIS, metformin decreased Ki67 by 40% overall (p=.06), by over 60% in ER+ve/HER2+ve DCIS (p=.004). and by 45% in PR+ve/HER2+ve DCIS (p=.02) There was no effect of metformin in HER2-ve DCIS, regardless of ER or PR status. Metformin did not affect Ki67 in DH overall, but showed a trend towards a decrease in women with abdominal adiposity (p-interaction=.05). Conclusions: Window of opportunity pre-surgical models provide insight into a drug’s preventive potential by targeting intraepithelial proliferations adjacent to invasive cancer. The model shows a high prevalence of preinvasive lesions (field cancerization) in apparently normal breast tissue adjacent to breast cancer. Metformin selectively decreased Ki67 in HER2+ve DCIS, particularly in the ER+ve subgroup, in line with a selective inhibitory effect on the HER2 pathway observed both in in vitro and in vivo preclinical models. Our results provide the background for a phase III trial of metformin in HER2+ve DCIS (ISRCTN16493703, Supported by AIRC, LILT and Health Ministry 2009-RF-153222). Citation Format: Bernardo Bonanni, Andrea DeCensi, Aliana Guerrieri-Gonzaga, Giancarlo Pruneri, Matteo Puntoni, Massimiliano Cazzaniga, Andrea Vingiani, Davide Serrano, Oreste Gentilini, Harriet Johansson, Valentina Aristarco, Matteo Lazzeroni, Clara Varicchio, Marilena Petrera, Giuseppe Viale. Metformin decreases Ki67 in HER2+ve ductal carcinoma in situ in a window of opportunity trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-12-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 5
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    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-01-16-P1-01-16
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-01-16-P1-01-16
    Abstract: Background: Consensus on the axillary management in cN+ breast cancer patients whoconvert to ycN0 after primary systemic treatment (PST) is still lacking. A surveywas conducted to investigate the clinical practice in this setting. Materials and Methods: A web-based survey was developed by a multidisciplinary group on behalfof the European Breast Cancer Research Association of Surgical Trialists (EUBREAST),and distributed to breast surgeons and radiation oncologists via breast cancersocieties. Results: We received 345 replies from 43 countries. A majority of responderssuggest FNA/CNB before treatment (81%) while 19 % perform histologic assessmentonly in selected cases. The preferred surgical approach to the axilla in cN1patients who convert to ycN0 is targeted axillary dissection (TAD) 55%,sentinel lymph node biopsy (SLNB) 21%, axillary lymphadenectomy (ALND) (level1-2) 19%, others 5%. When SLNB is preformed, single and dual tracers are usedin 62% and 38% respectively. No minimumnumber of SLNs is required by 36 % of the surgeons, while 8% and 56% suggest toremove at least 2 or 3 SLNs respectively.For targeted lymph node biopsy (TLNB) or TAD, there is a wide heterogeneitywith regards to localization techniques. In case of multiple suspicious nodes, 65%of the responders declared to mark only one node. 47 % of responders routinelyperform an additional preoperative localization of the TLN. Imaging modalitiesto assess the ycN status are: ultrasound (67%), MRI (21%), other(12%). In caseof ambiguous finding before PST (cN+) ALND was suggested by 23 % only after routine histologicconfirmation of lymph node involvement and by 45 % without. 29% of theresponders perform SLNB/TAD/TLNB without additional axillary surgery 3%suggested different approaches. 66 % of the participants recommended ALND in ycN+ patients only after furtherhistologic confirmation, while 23 % do not perform CNB/FNA. 11 % voted forTAD/SLNB/TLNB in this setting. The decision for post-operative regionalirradiation is influenced by initial nodal lymph node status (61 %) and by acombination of pre- and post- PST assessment (39%). 21% of the responders neverirradiate level I in patients with a ypN & gt;1 status after ALND while 37 % suggestselective use of RT and 42 % favoured RT in all patients. Target volumes forelective nodal irradiation are determined mainly based on ESTRO (61%) and RTOG(32%) guidelines.In case of macrometastatic nodal disease (ycN0ypN+) regional nodeirradiation was suggested by 59 % of the participants regardless of the numberof involved nodes. 37 % suggested RT in patients with more than 3 positive nodes,while 4% would never irradiate. After a positive TAD or SLNB radiationoncologists suggest ALND in 63 % and RT in 37%. Similar results were attainedfor ypN1mi and ypN0(i+). 34 % of the breastsurgeons suggested ALND for patientswith ypN1(mi) status after TAD/SLNB, 31 % favored RT, 23% a combination and 12%suggested omission of further reginal treatment. Remodeling fibrotic scarsrarely affect regional treatment planning. Conclusions: The results of this EUBREAST survey highlightthe wide heterogeneity in the approach to the axilla after PST, corroborate theneed for further clinical research and provide the rationale for the AXSANA(EUBREAST 3) study . Supporting Societies:. American Society of Breast Surgeons (ASBrS). Arbeitsgemeinschaft für gynäkologische Onkologie (AGO). Associazione Nazionale Italiana Senologi Chirurghi (ANISC). Collegio Italiano dei Senologi. Deutsche Gesellschaft für Radioonkologie (DEGRO). Deutsche Gesellschaft für Senologie (DGS). Global Breast Hub. Israel Breast Surgeons Society. Israel Radiation Therapy society. Swiss Society of Senology (SSS). Scuola Italiana di Senologia. Società Polispecialistica Italiana Giovani Chirurghi (SPIGC). Swedish Breast Cancer Group. The Oncoplastic Breast Consortium (OPBC) Citation Format: Maria Luisa Gasparri, Jana De Boniface, Oreste Davide Gentilini, Orit Kaidar-Person, Philip Poortmans, Thorsten Kuehn. Perspectives on axillary management after primary systemic treatment: An international EUBREAST survey [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-16.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. GS4-02-GS4-02
    Abstract: Background: Data on the oncologic safety of omission of axillary lymph node dissection (ALND) in node positive (N+) patients who downstage to ypN0 with neoadjuvant chemotherapy (NAC) is sparse. Additionally, there is no consensus on which axillary staging procedure should be used in this setting, sentinel lymph node biopsy (SLNB) alone or in combination with localization and retrieval of the clipped positive node, also known as targeted axillary dissection (TAD). Whether the reduction in the false negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. We sought to evaluate oncologic outcomes after omission of ALND in a large, real-world cohort of breast cancer (BC) patients and to compare rates of axillary recurrence after SLNB with dual tracer mapping vs. TAD. Methods: Data were collected from 19 centers in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 BC who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumor or isolated tumor cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 785 patients (565 treated with SLNB and 220 with TAD) treated with NAC followed by surgery from 01/2014-12/2020. Median patient age was 50 years. The majority (57%) of patients had clinical T2 tumors, and 95% had N1 disease. Most (55%) were HER2+, and 21% were triple negative. Most patients (81%) received anthracycline and taxane-based chemotherapy regimens, but NAC regimens differed between patients treated with TAD and those treated with SLNB (Table 1). All patients with HER2+ tumors received anti HER2 therapy. Nodal radiotherapy was administered to 76% of patients, and was more common in patients who underwent TAD (82% TAD vs 74% SLNB, p=0.017). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (80% TAD vs. 66% SLNB, p & lt; 0.001). TAD localization was with wire in 46%, radioactive seed in 40%, ultrasound in 5%, tattoo in 2%, and with a combination of these techniques in 7%. The clipped node was successfully retrieved in 94% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group [3 (IQR 3-5) vs 4 IQR 3-5), p & lt; 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p & lt; 0.001] (Table 1). The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.1% (95%CI 0.39-2.4%), 3.1% (95%CI 1.6-5.3%) and 10% (95%CI 7.6-13%), respectively. The two-year cumulative incidence of axillary recurrence did not differ between patients treated with TAD compared to SLNB (0% vs 0.9%, p=0.19). Conclusion: Early axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly lower in TAD than SLNB. Although longer follow-up is needed to confirm these findings, the main advantage of TAD seems to be a reduction in the number of lymph nodes removed. Overall, these results support omission of ALND in patients who successfully downstage to node negative disease after NAC. Table 1: Clinicopathological Features of the Study Cohort, Stratified by Axillary Staging Technique Citation Format: Giacomo Montagna, Mary Mrdutt, Astrid Botty, Andrea V. Barrio, Varadan Sevilimedu, Judy C. Boughey, Tanya L. Hoskin, Laura H. Rosenberger, E Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Diaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Maria Del Rosario Cueva Perez, Marcelo Chavez Diaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis Resende Paulinelli, Sebastian Sole Zarhi, Sherko Küemmel, Simona Bruzas, Simona Di Lascio, Tamara Parissenti, Uwe Güth, Valentina Ovalle, Christoph Tausch, Monica Morrow, Thorsten Kühn, Walter P. Weber. Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-02.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. OT1-07-01-OT1-07-01
    Abstract: Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 36 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative ( & lt; 10% positive cells in IHC) and PgR-negative ( & lt; 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2023 -Primary outcome analysis: Q1/2027 Current accrual: In June 2022, 150 patients were recruited in Germany and Italy. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy) Citation Format: Toralf Reimer, Thorsten Kuehn, Angrit Stachs, Anke Kleine-Tebbe, Nikola Bangemann, Andrea Stefek, Carolin Hammerle, Jörg Heil, Antje Nixdorf, Gabriele Bonatz, Agnieszka Nolte, Isabel T. Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Davide Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-07-01.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. OT3-12-01-OT3-12-01
    Abstract: Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy Maria Luisa Gasparri1, Ilary Ruscito2, Filippo Bellati2, Fabio Corsi3, Rosa Di Micco4, Oreste D. Gentilini4, Thorsten Kuehn5, Andrea Papadia1, Donatella Caserta2, Lorenzo Rossi6, Arianna Calcinotto7 1 Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale, Ospedale Regionale di Lugano, Lugano, Switzerland 2 Department of Medical and Surgical Science and Translational Medicine, Sapienza University of Rome, Azienda Ospedaliera Sant’Andrea, Rome, Italy 3 Breast Unit, Department of Surgery, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", Università di Milano, Milan, Italy 4 Breast Surgery Unit, San Raffaele University Hospital, Milan, Italy 5 Interdisciplinary Breast Center, Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany 6 Oncology Institute of Southern Switzerland, Bellinzona, Switzerland 7 Cancer Immunotherapy lab, IOR Institute of Oncology Research, Bellinzona, Switzerland Background: Almost 20% of breast cancer patients present at diagnosis with clinically positive nodes. Most of these patients undergo neoadjuvant therapy in order to de-escalate the axillary surgery in case of response (sentinel lymph node biopsy, targeted axillary dissection or targeted axillary dissection, instead of an axillary lymphadenectomy). The conversion from positive to negative nodes after neoadjuvant therpy is expected in approximately the 60% of the cases, depending by tumor subtypes. Several models have been proposed with the goal of identifying predictors of nodal response prior to neoadjuvant treatment. The immune system plays a pivotal role in cancer invasion and progression. Its role in treatment response is currently under investigation in several settings. Primary endpoint: to identify a preoperative immune profiling of breast cancer patients with nodal involvement at diagnosis and to correlate the immune changes after neoadjuvant therapy with the nodal response (macrometastases, micrometastasis, isolated tumor cells, complete response). Trial design: It is an international prospective cohort study including breast cancer patients undergoing standard neoadjuvant therapy, who present initially with biopsy-proven axillary lymph node metastasis. Ten immune markers will be analyzed using immunohistochemistry and tissue microarray in primary tumor and nodal tissue samples (tumor associated neutrophils, CD4 lymphocytes, CD8 lymphocytes, T regulatory cells, Macrophages, Follicular dendritic cells(DC), plasmocytoid DC, interdigitant DC, mature DC, Lysosomal associated membrane protein 3). The tissue analysis will be performed on the biopsy collected at diagnosis (prior to neoadjuvant therapy) and during the axillary surgery (after neoadjuvant therapy). Target accrual/sample size: 210 patients Statistical analysis: To compare the distribution of immune cells according to the state of lymph node metastasis, Student’s t test will be performed. Pearson’s chi-square test will be used to evaluate the correlation between immune profile and nodal response, based on clinic-pathological features. Odds ratios (ORs) and 95% confidence intervals (CIs) will be calculated using logistic regression analysis. Multivariable analysis will be performed using the multivariable logistic regression model. Logistic regression models will be used to identify the clinical, pathologic and immunological variables associated with the nodal response. P-values less than 0.05 will be considered significant. Analyses will be performed using Microsoft IBM SPSS® version 20.0 for Mac. Current status: Recruitment has not started yet. Contact information: marialuisa.gasparri@eoc.ch Citation Format: Maria Luisa Gasparri, Ilary Ruscito, Filippo Bellati, Fabio Corsi, Rosa Di Micco, Oreste Davide Gentilini, Thorsten Kuehn, Andrea Papadia, Donatella Caserta, Lorenzo Rossi, Arianna Calcinotto. Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-12-01.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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