Node-positive Patients Research Articles

Abstract P3-05-03: Long-term survival and intra-tumor heterogeneity of progesterone receptor expression in estrogen receptor-positive/progesterone receptor-positive premenopausal women with breast cancer

Abstract Background: Women with estrogen receptor (ER)-positive disease have a long-term risk of distant recurrence. The poor survival of premenopausal women diagnosed with breast cancer combined with the otherwise long life expectancy makes it especially important to identify tumor characteristics associated with long-term survival. Intra-tumor heterogeneity, having cancer cells of varying characteristics across the tumor, may promote therapeutic resistance and metastatic capacity. We have previously shown that high intra-tumor heterogeneity of ER increases the risk of fatal breast cancer. To our knowledge, the relation between intra-tumor heterogeneity of progesterone receptor (PR) expression and long-term survival is not known. We aimed to study the association between intra-tumor heterogeneity of PR and long-term survival of premenopausal women in the Stockholm tamoxifen trial (STO-5), with 20-years complete follow-up. Methods: This study was a secondary analysis of 504 ER-positive/PR-positive premenopausal women from the STO-5 trial (1990-1997). 451 women had human epidermal growth factor receptor 2 (HER2)-negative tumors. Patients were randomized to receive either 2 years of endocrine treatment (tamoxifen and/or goserelin) or no endocrine treatment. Lymph node-positive patients (n=251) also received standard chemotherapy (CMF). Immunohistochemical analysis, including estimating the proportion of tumor cells for each PR intensity level (0, 1+, 2+, or 3+), was completed in 2020. Intra-tumor heterogeneity of PR was calculated using Rao’s quadratic entropy and then categorized into low and high intra-tumor heterogeneity groups, using a predefined cutoff at the second tertile. Complete long-term (20 year) follow-up was obtained from high-quality Swedish registries. Long-term distant recurrence-free interval (DRFI) was assessed using univariate Kaplan-Meier analysis and multivariable Cox proportional hazard modeling, adjusting for patient and tumor characteristics. Results: A statistically significant difference in 20-year DRFI was seen between patients with high and low intra-tumor heterogeneity of PR in the univariate Kaplan-Meier analysis (log-rank P< 0.01). Survival proportions for DRFI at 20 years were 60.2% (95% CI, 53.2%-68.1%) and 73.3% (95% CI, 68.6%-78.3%) for patients with high and low PR intra-tumor heterogeneity, respectively. Analysis in patients with HER2-negative tumors yielded similar results. In the multivariable analysis, women with high intra-tumor heterogeneity of PR had a significantly increased long-term risk of distant recurrence, compared to women with low intra-tumor heterogeneity, hazard ratio (HR)=1.49 (95% CI, 1.08-2.06). The same pattern was seen in HER2-negative women, HR=1.50 (95% CI, 1.06-2.12), see Table. Conclusions: This study suggests an increased long-term risk of distant recurrences in ER-positive/PR-positive premenopausal women with high intra-tumor heterogeneity of PR as compared to women with low intra-tumor heterogeneity of PR, independent of HER2 status. Ongoing analyses include using deep learning for image analysis of breast cancer tumors to examine intra-tumor heterogeneity at higher resolution and for various tumor characteristics. Better understanding of tumor characteristics associated with long-term risk in premenopausal women is needed, given the poor prognosis and early onset of the disease. Long-term risk of distant recurrence by PR intra-tumor heterogeneity and HER2 status Multivariable Cox proportional hazard regression modeling of 20-year distant recurrence-free interval (DRFI) by high and low PR intra-tumor heterogeneity. ER-positive/PR-positive and ER-positive/PR-positive/HER2-negative premenopausal women were analyzed separately. The crude model was adjusted for age, randomization year, lymph node status, and endocrine treatment. The full model was adjusted for age, randomization year, lymph node status, endocrine treatment, tumor size, Ki-67 status, and HER2 status. Citation Format: Oscar Danielsson, Huma Dar, Gizeh Perez-Tenorio, Anna Nordenskjöld, Christina Yau, Christopher C. Benz, Laura J. Esserman, Bo Nordenskjöld, Olle Stål, Tommy Fornander, Annelie Johansson, Linda S. Lindström. Long-term survival and intra-tumor heterogeneity of progesterone receptor expression in estrogen receptor-positive/progesterone receptor-positive premenopausal women with breast cancer [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 P3-05-03.

Abstract P3-05-02: Trends in clinical treatment of early stage ER+PR- breast cancer in the National Cancer Database

Abstract Background Estrogen receptor positive (ER+) progesterone receptor negative (PR-) tumors are a distinct subset of breast cancers that are not well characterized. It is critical to better understand the biology of ER+PR- tumors and tailor therapy accordingly for this unique subgroup. The objective of this study is to compare the ER+PR- subgroup of breast cancer as compared to the double positive ER+PR+ group in a large, well-characterized database to determine if the tumors that are PR- are associated with higher rates of genomic testing and chemotherapy receipt. Methods We identified patients diagnosed with ER+Her2-, Stage 1-3 invasive breast cancer from 2010-2015 in the National Cancer Database. We excluded patients who received neoadjuvant therapy. Demographics and clinical characteristics for the ER+PR+ and ER+PR- groups were obtained. Differences between groups were assessed using the chi-square test. Multivariable logistic regression analysis was performed on both the node negative and node positive patients in order to identify factors independently associated with having a genomic test and receiving chemotherapy in the ER+PR+ and ER+PR- cohorts. Results Of the 363,945 eligible patients, 327,357 (89.9%) patients had ER+PR+ breast cancer and 36,588 (10.1%) had ER+PR- breast cancer. A trend towards larger tumor size in the ER+PR- population as compared to the ER+PR+ population was noted with 23.1% vs 17.3% of tumors 2-5cm and 2.2% vs 1.2% of tumors > 5cm, respectively. Higher grade was also seen in the ER+PR- group as compared to the ER+PR+ group with 27.1% versus 11.7% grade 3 tumors. In both the node negative and node positive populations, genomic testing was less likely to be sent on a PR- breast cancer than a PR+ breast cancer. When genomic testing was sent, there were more high risk Oncotype Recurrence scores (RS > 30) in the PR- group than the PR+ group. For node negative breast cancer high risk Oncotype recurrence scores were found in 32.4% of the ER+PR- population versus 5.6% in the ER+PR+ population. In the node positive cohort high risk Oncotype Recurrence scores were seen in 27.8% of the ER+PR- population as compared to 5.0% in the ER+PR+ population. Patients with discordant ER+PR- breast cancer were more likely to receive chemotherapy than their ER+PR+ counterparts in both the node negative cohort (32.2% vs 12.7%) and the node positive cohort (73.2% vs 64.5%). Conclusion There have been limited studies to date specifically focused on the ER+PR- subgroup. Patients with ER+PR- breast cancer have a higher grade, larger size, higher risk genomic testing, and are more likely to receive chemotherapy than their ER+PR+ counterparts. Discordance in hormone receptor status contributes to a more aggressive type of breast cancer that may impact clinical and treatment decisions. Citation Format: Poornima Saha, Angeline Yu, Priya Thakkar, Kristine Kuchta, Katharine Yao. Trends in clinical treatment of early stage ER+PR- breast cancer in the National Cancer Database [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 P3-05-02.

Abstract GS5-12: Hypofractionated Radiotherapy in patients with Breast Cancer (HRBC): Acute toxicity data of a phase III randomized study

Abstract Background HRBC is a phase III randomized open label study of adjuvant radiotherapy in patients with breast cancer. In this study we compared a 3 weeks radiation schedule with 2 weeks. Materials and methods Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomized to 34Gy in 10 fractions over 2 weeks (study arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (control arm). Boost dose when indicated was 8Gy/2# in both the arms. Patients were planned on simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using a RTOG grading system. Assessment was carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using Harvard/NSABP/RTOG scale. The toxicity between the two arms was compared using Fisher’s exact test. The trial was approved by institutional ethics committee. This trial is registered with ClinicalTrials.gov, number NCT04075058. Results This study included 1121 patients. Median follow up was 35 months (range 6-84 months). Mean age was 48 year (range 24-80 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3 week arm and more node positive patients in the 2 week arm. There were more oestrogen receptor positive tumors in the 3 week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 98(17%) and 82(15%); and 16(3%) and 10(2%) in the 3 week and 2 week arm (p=0.15), respectively. Cosmetic outcome was significantly better in 2 week arm 94% as compared to 90% in the 3 week arm (p=0.016). Conclusion The two radiation schedules were comparable in terms of acute skin toxicity. Cosmetic outcome was better in the 2 week schedule. Citation Format: Budhi Singh Yadav, Divya Dahiya, Manish Gupta. Hypofractionated Radiotherapy in patients with Breast Cancer (HRBC): Acute toxicity data of a phase III randomized 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 GS5-12.

Abstract GS4-02: 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 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< 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< 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p< 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.

Abstract P1-04-15: Clinical application of 21-gene breast-cancer assay (Oncotype DX) in early hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer with Lymph-Node-Positive Disease

Abstract The 21-gene breast-cancer assay (Oncotype DX) has become widely available since 2011 and it is incorporated in treatment guidelines for early hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. The Rxponder trial shows the role of adjuvant chemotherapy in node positive patients with a RS score less than 25, but in patients under 50 years of age benefit from adjuvant chemotherapy treatment regardless of the Oncotype. We analyzed our results of the Oncotype Dx in 317 node positive hormone-receptor–positive, HER2-negative early breast cancer patients, performed as a clinical practice since 2015 to 2020. The aims to current study are to examine the clinical significance of the oncotype Dx results in this specific population. The median age was 59 years with 102 patients (32%) less than 50 years. Median Oncotype DX score was 18 ( 1–68), RS< 25 in 247 (78%) and RS>25 in 70 (22%) patients. Median initial tumor size was 20 mm and the expression of classical biological variables was: median estrogen and progesterone receptors by immunohistochemistry 276 and 139 respectively and median Ki67 index was 23%. 145 patients received chemotherapy treatment (45,7%), (RS < 25:32%, RS>25: 94%) with a 63% of the patients in the group less than 50 years of age in contrast to 36% in patients with more than 50 years. Patients with more than 50 years have less RS score (median 18 ) than patients less than 50 years (median 21 ). With a median of follow up of 45 month with achieved a total of 29 recurrence (9,1%), RS< 25: 8% and RS>25 13%. The estimated median disease free survival of patients with RS< 25 was 111 in contrast to 97 in patients with RS>25 (log rangk : p:0,035) and without differences according with age of the patients. In axillary node positive patients, Oncotype Dx could avoided chemotherapy in 55% of patients, with a index of recurrence of 9%. Patients with a RS score greater than 25 have a higher rate of recurrence (13%) despite the fact that the majority (94%) received treatment with chemotherapy. Improve adjuvant treatment is needed in patients with a score greater than 25. Citation Format: Ariadna Gasol Cudós, Serafin Morales Murillo, Noemí Tuset Der-Abrain, Ana Velasco Sánchez, Felip Vilardell Villellas, Douglas Sánchez Guzmán, Carles Canosa Morales, Jordi Melé Olivé, Laura Arbones Cid. Clinical application of 21-gene breast-cancer assay (Oncotype DX) in early hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer with Lymph-Node-Positive Disease [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 P1-04-15.

Abstract OT1-08-01: AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with clinically axillary lymph node involvement metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR23, Lymph-ICF and SOC 13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 2347 patients from 247 study sites and 23 countries were enrolled in the study between June 2020 and June 2022. Among 1804 patients with a defined surgical concept 758 women were scheduled for ALND, 722 for TAD, 232 for SLNB, 16 for TLNB and 19 for other procedures. A target lymph node was marked in 1215 patients, most frequently using clips/coils (982, 82.0%), followed by magnetic seeds (100, 8.4%), carbon ink (99, 8.3%), radar marker (21, 1.8%), radioactive seeds (5, 0.4%), and other techniques (8, 0.7%). Citation Format: Thorsten Kühn. AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [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 OT1-08-01.

Abstract P2-10-02: Impact of neoadjuvant treatment on the accuracy of breast MRI and calliper in premenopausal ER-positive, HER2-negative, and node-positive breast cancer patients: Prospective phase III clinical trial

Abstract Background: Improved understanding of factors affecting the accuracy of breast MRI after NST can lead to more tailored use of MRI in deciding surgical extent after NST. Purpose: To investigate whether the accuracy of magnetic resonance imaging (MRI) and caliper predicting residual tumor extent is affected by neoadjuvant treatment in estrogen receptor (ER) positive and HER2-negative, lymph node-positive, premenopausal breast cancer breast cancer. Materials and Methods: We analyzed the imaging and clinicopathologic data of 123 patients in phase 3, randomized clinical trial (NCT01622361), which compared neoadjuvant chemotherapy (NCT) with neoadjuvant endocrine therapy (NET) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), lymph node (LN)-positive, premenopausal breast cancer patients. In this study, we compared the largest size of MRI and Caliper after neoadjuvant treatment with one of pathology. Results: In patient with discrepancy in predicting response to NST, the measurement (MRI or caliper) that predict as non-response (SD or PD) was more accurate in both of NCT and NET group (ICC, Intraclass correlation coefficient, MRI; 0.84, 95% CI 0.616-0.942, Caliper;0.75, 95% CI 0.303-0.931). The accuracy of MRI was better in NCT group than in NET group (ICC 0.86; 95% CI 0.626-0.956 for NCT, 0.47; 95%CI 0.133-0.708 for NET). The mean absolute discrepancies (largest size by MRI or caliper -largest size in pathology) for the MRI and Caliper were, respectively, -0.78cm and -1.04cm in NCT group and -0.44cm and -1.32cm in NET group (p > 0.05). The proportion of discrepancy >1cm or >0.5cm were not significantly difference between NCT and NET groups among MRI and Caliper. Conclusion: In ER-positive, HER2-negative, lymph node-positive breast cancer, both MRI and caliper tend to overestimate residual tumor size than pathology in NET group compare to NCT group. When MRI and caliper show discrepancy in predicting response to NST, the measurement (MRI or caliper) that predict as non-response (SD or PD) was more accurate in both of NCT and NET group. These factors should be considered for deciding the evaluation method of response and surgical decision after NST and surgical decision in this subgroup. REGISTRATION: ClinicalTrials.gov identifier: NCT01622361 Citation Format: Sungchan Gwark, Sei Hyun Ahn, Jong Won Lee, Byung Ho Son, Beom Seok Ko, Jisun Kim, Il-Yong Chung, Sae Byul Lee, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim, Hee Jin Lee, Gyungyub Gong, Hee Jeong Kim. Impact of neoadjuvant treatment on the accuracy of breast MRI and calliper in premenopausal ER-positive, HER2-negative, and node-positive breast cancer patients: Prospective phase III clinical trial [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 P2-10-02.

Abstract CC1-1-2: To clip or not to clip (Part 2)

Abstract Neoadjuvant chemotherapy (NAC) changed the breast surgery approach and increased indications in recent years. NAC allows to downstage the primary tumor and also may clear the axilla of lymph node metastases in some patients. In fact, NAC allows de-escalation of surgery: not only resulted in an increase in conservative surgery in 40%, which was the initial goal of chemotherapy, but in particular it allows for a reduction in axillary surgery. Furthermore, in relation to the molecular characteristics of the tumors we can have a pathological complete response (pCR) ranging from 20 to 80%. In node-positive patients who converted to cN0 different prospective studies ACOSOG Z1071, SENTINA, SN FNAC and GANEA 2, have demonstrated that the FNR of the SNB was high, more than the acceptable 10%. Therefore, strategies to reduce the FNR treatment in cN+ patients are being investigated: is to remove more than three negative axillary lymph nodes or marking of positive axillary nodes with a tattoo or clip, the so-called target axillary dissection (TAD), to document their removal. But all the effort to reduce the FNR rate do not have clinical prognostic significance. This has already been demonstrated in the literature in different randomized trials with long term follow up. The 10-year follow-up of our study confirmed our preliminary data that the use of standard sentinel node biopsy (SNB) without the use of clip is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome. In fact, the axillary recurrences found were less than 2% in particular in the group that started from a positive axilla were 1.8 %, if we considered that 2 of them had a micrometastatic SN and refused the AD, but if we considered only those with a negative SN the percentage drops to 0.9% Similar positive data with different follow up were also confirmed by other studies that used SNB alone without TAD. All these studies data, with now comforting results on the follow up, confirm that SN surgery alone for selected patients who have an excellent response to NAC is not oncologically inferior to AD during a short- and long-term follow-up. Citation Format: Viviana Galimberti. To clip or not to clip (Part 2) [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 CC1-1-2.

Oncologic outcomes in breast cancer patients with metastatic nodes and pathological nodal response following neoadjuvant chemotherapy without axillary dissection: a literature review.

With promising nodal pathological complete response (pCR) after neoadjuvant chemotherapy, the role of axillary lymph node dissection (ALND) was questioned. While there is much data on the accuracy of axillary staging after neoadjuvant chemotherapy to predict nodal pCR, limited data on the oncological safety of omitting ALND exists. We aim to review the oncological safety of omitting ALND in patients with initially metastatic nodes achieving nodal pCR, based on axillary staging, following neoadjuvant chemotherapy. A PubMed search of relevant articles from 1st January 2013 to 15th September 2022 was performed. Studies with duplication of patients, ALND only, no oncological details, initially N0 patients only and patients without nodal pCR were excluded. Fifteen studies with 1,515 eligible patients (range, 29-242 patients) were analysed. There was heterogeneity of patients among the included studies and patients had varying TN staging, making selection criteria for omission of ALND inconclusive. Sentinel lymph node biopsy (SLNB) was the most studied mode of axillary staging in 1,416 (93.5%) patients, though 35.7% had <3 SLN harvested. On average median follow-up of 52.8 months (range, 9-110 months), axillary recurrence ranged from 0% to 3.4%. There was limited data on survival outcomes. In node positive breast cancer patients who achieved nodal pCR after neoadjuvant chemotherapy, the axillary recurrence rate was low without ALND. However, survival data was limited. The selection criteria and ideal axillary staging technique for patients, who are suitable for axillary preservation, are unclear. More prospective studies with longer follow-up, providing survival data, are needed.

Abstract CC1-1-1: To clip or not to clip (Part 1)

Abstract Clinically node positive breast cancer patients often recieve neoadjuvant chemotherapy which can eradicate nodal disease. While sentinel node dissection alone has been shown to predict treatment response with a false negative rate of 12-14%, it is possible to increase the accuracy by performing targeted axillary dissection (TAD). To perform TAD, a clip is placed in a node if biopsy confirms disease. The procedure then involves selectively localizing and removing the clipped node in addition to the sentinel nodes. Multiple studies have show that this approach has a false negative rate of &amp;lt;5%. These studies also show that the clipped node is not retrieved as a sentinel node in &amp;gt; 20% of cases. This means that evaluating the sentinel nodes alone would miss evaluating the node with confirmed disease in a significant proportion of patients. This session will focus on the question of whether there is benefit to placing clips in nodes and ensuring removal after neoadjuvant chemotherapy. Citation Format: Abigail Caudle. To clip or not to clip (Part 1) [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 CC1-1-1.

Abstract P4-02-06: Clinical and biological predictors of lymph node involvement in patients with early breast cancer for adjuvant treatment personalization

Abstract Background: Over the last years, the management of patients with node positive early breast cancer has gone through important innovations. On the medical side, new targeted therapies such as olaparib and abemaciclib have been introduced, with promising results on the invasive disease-free survival. Moreover, sparing axillary lymph node dissection has proven to be noninferior in terms of overall survival. However, no tools are currently available to predict lymph node involvement before definitive surgical evaluation. The aim of the study was to analyze clinical and pathological characteristics of patients with node positive early breast cancer to explore potential risk profiles associated with a ≥3 nodal involvement. Methods: The study retrospectively analyzed 335 node-positive breast cancer patients treated at the Breast Unit of the CRO Aviano National Cancer Institute, between 2017 and 2021. Data regarding primary tumor biological features, lymph node involvement and surgical approach were collected. Associations between clinico-pathological characteristics and ≥3 lymph node involvement were tested through stepwise logistic regression and the gradient boosting machine learning algorithm (GBM). Results: Among the 335 analyzed patients, 87.0% had a primary tumor &amp;lt; 5 cm, with a single positive lymph node in 73.3% of cases. Hormone receptors were mainly positive (respectively 93.5% and 83.4% for estrogen and progesterone receptors). Tumor grade was most frequently well differentiated (Grade 1 in 60.7%), with a Ki67 &amp;lt; 20% (59.5%). After multivariable logistic regression, a tumor size ≥ 3 cm (OR 3.24, CI95% 1.47-7.17, p = 0.004), the presence of massive lymphovascular stromal invasion (OR 2.50, CI95% 1.02-6.14, p = 0.045) and 2 or more positive sentinel lymph nodes at surgical evaluation (OR 6.08, CI95% 3.34-11.05, p &amp;lt; 0.001) were associated with a higher risk of identifying ≥ 3 positive lymph nodes after subsequent axillary dissection. Similar results were observed in the luminal-like cohort. A GBM machine learning model was then developed with a 0.77 Area Under the Curve. Features with the highest relative importance (RI) were single sentinel node involvement (RI 16.1873), followed by tumor size ≥ 3 cm (RI 10.2024), ≥2 positive sentinel lymph nodes (RI 8.5050) and lymphovascular stromal invasion (4.0217). Consistently, number of positive sentinel lymph nodes and tumor size were the predominant features in all top 20 GBM models. Conclusions: The present study explored the definition of risk profiles linked to 3 or more positive lymph nodes based on clinical and pathological features. It, moreover, tested the feasibility of developing machine learning classifiers to support future clinical decision-making. Due to the growing complexity of the adjuvant setting, finding a balance between minimally invasive surgical and staging approaches and risk definition for treatment personalization will become increasingly critical. Citation Format: Tania Pivetta, Brenno Pastò, Martina Urbani, Elisabetta Benozzi, Nicola De Pascalis, Tiziana Perin, Mario Mileto, Bruno Pasquotti, Erica Piccoli, Lorenzo Vinante, Chiara Bampo, Silvia Bolzonello, Mattia Garutti, Milena Nicoloso, Serena Corsetti, Simona Scalone, Lucia da Ros, Paola di Nardo, Camilla Lisanti, Simon Spazzapan, Barbara Belletti, Michele Bartoletti, Lorenzo Gerratana, Samuele Massarut, Fabio Puglisi. Clinical and biological predictors of lymph node involvement in patients with early breast cancer for adjuvant treatment personalization [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 P4-02-06.

Abstract P2-03-11: Differential Long-Term Benefit from Adjuvant Tamoxifen Therapy in Estrogen Receptor (ER)-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Premenopausal and Postmenopausal Breast Cancer Patients

Abstract Background: Tamoxifen is a standard endocrine therapy for both pre- and postmenopausal ER-positive breast cancer patients. Patients with ER-positive disease have a long-term risk of distant recurrence, thus, long-term follow-up studies are essential to understand true treatment benefit. Clinically used tumor characteristics are prognostic 5-10 years after primary diagnosis, however, whether these characteristics are predictive of long-term tamoxifen benefit is largely unexplored. Therefore, we aimed to determine the long-term tamoxifen therapy benefit by the clinically used tumor characteristics in pre- vs postmenopausal patients in the Stockholm tamoxifen (STO)-trials with 20-years complete follow-up. Methods: Secondary analysis of 1242 ER-positive/HER2-negative patients from the STO-trials, randomized to at least 2 years of 40 mg tamoxifen vs no endocrine therapy (control). Premenopausal lymph node-positive patients were allocated to chemotherapy as standard of care and postmenopausal high-risk patients were further randomized to chemotherapy vs radiotherapy. Tumor immunohistochemical analysis was recently conducted. Complete 20-year follow-up was obtained from Swedish high-quality registries. Long-term distant recurrence-free interval (DRFI) was assessed by multivariable Cox proportional hazard regression and time-varying analysis using flexible parametric modelling. Results: Premenopausal patients showed significantly improved long-term DRFI from tamoxifen vs control if they were lymph node-negative (Hazard Ratio [HR]=0.46; 95% CI, 0.24-0.87), PR-positive (HR=0.61; 95% CI, 0.41-0.91), or of genomic low risk (HR=0.47; 95% CI, 0.26-0.85), see Table. In postmenopausal patients, significantly improved long-term DRFI from tamoxifen vs control was seen for all good prognosis tumor characteristics, i.e. small tumor size (pT≤20mm: HR=0.55; 95% CI, 0.39-0.77), tumor grade 1-2 (HR=0.55; 95% CI, 0.41-0.73), lymph node-negative (HR=0.44; 95% CI, 0.30-0.64), PR-positive (HR=0.60; 95% CI, 0.44-0.80), Ki-67-low (&amp;lt; 15%: HR=0.51; 95% CI, 0.38-0.68), and genomic low risk (HR=0.53; 95% CI, 0.37-0.74), see Table. Also, postmenopausal patients with large tumor size (pT&amp;gt;20mm: HR=0.64; 95% CI, 0.44-0.94) and PR-negative tumors (HR=0.51; 95% CI, 0.32-0.81) showed significant long-term tamoxifen benefit. Time-varying analysis in premenopausal patients indicated that tamoxifen therapy benefit diminished over time. Significant tamoxifen benefit until year 5, 10, and 15 after primary diagnosis was observed for PR-positive, lymph node-negative, and genomic low-risk patients, respectively. Postmenopausal patients had a significant long-term tamoxifen benefit if they had tumors of small or large tumor size, tumor grade 1-2, lymph node-negative status, PR-positive status, low Ki-67 levels, or genomic low risk. Conclusions: This study suggests a differential long-term tamoxifen therapy benefit in pre- vs postmenopausal patients. Clinically defined low-risk postmenopausal patients have long-term tamoxifen benefit, whereas the benefit is absent or diminish over time for premenopausal patients. Improved long-term prognostic and endocrine therapy predictive markers in premenopausal breast cancer patients with poor prognosis and long life-expectancy is needed, which could involve molecular tools. Long-term tamoxifen benefit in premenopausal and postmenopausal breast cancer patients by the clinically used tumor characteristics. Table Multivariable Cox proportional hazard regression analysis of 20-year distant recurrence-free interval (DRFI) for patients with ER-positive/HER2-negative tumors, comparing patients randomized to tamoxifen vs patients randomized to no endocrine therapy (control). Adjusted for age, randomization year, tumor size, tumor grade, lymph node status, PR status, Ki-67 status, chemotherapy, radiotherapy, and type of surgery. Citation Format: Annelie Johansson, Huma Dar, Anna Nordenskjöld, Gizeh Perez-Tenorio, Christina Yau, Christopher C. Benz, Laura J. Esserman, Laura Van’t Veer, Bo Nordenskjöld, Olle Stål, Tommy Fornander, Linda S. Lindström. Differential Long-Term Benefit from Adjuvant Tamoxifen Therapy in Estrogen Receptor (ER)-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Premenopausal and Postmenopausal Breast Cancer Patients [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 P2-03-11.

Abstract P2-14-19: Targeted Axillary Lymph Node Dissections Using Radar Reflector Localization Can Reduce Unnecessary Axillary Lymph Node Dissections in Node Positive Patients Treated with Neoadjuvant Chemotherapy

Abstract Background Targeted axillary dissection (TAD) is a surgical strategy that involves staging the axilla through sentinel lymph node biopsy (SLNB) combined with the removal of a biopsy-proven positive lymph node identified by a clip. TAD reduces the false negative rate of SLNB alone in patients with clinically detected nodal metastasis who receive neoadjuvant chemotherapy (NAC) while avoiding axillary lymph node dissections (ALND). Radar reflector-localization (RRL) can be used to identify previously positive nodes and safely and effectively guide dissection. Methods We performed an institutional retrospective chart review of breast cancer patients with clinical stage T1-3 and N1-3 disease treated with NAC from 2015 to 2020 who had a biopsy proven positive node and underwent TAD using RRL. The primary outcome was the retrieval of clipped node as documented by gross visualization or specimen radiography. Secondary outcomes included pathologic complete response rates and completion axillary lymph node dissections (cALND). Results 79 patients were identified who fulfilled inclusion criteria. 32 (40.5%) had RRL markers placed prior to chemotherapy (mean 187 days prior to surgery) and 47 (59.5%) had RRL markers placed following the completion of chemotherapy (mean 7 days prior to surgery). The clipped node was retrieved in 77 patients (97.5%). 32 of the 34 ypN0 (i+) patients avoided an ALND; 1 patient had a cALND for failure to localize the RRL and 1 patient had a cALND for a false-positive on frozen section. There was no significant difference in clip recovery rates in the pre vs post NAC RRL groups (p=1.00). Conclusion RRL systems are an effective way to guide TAD with a high success rate in identifying and removing previously biopsied nodes. These markers can be placed prior to NAC without migration or deactivation. This strategy allows surgeons to avoid unnecessary cALND. Citation Format: Lilia Lunt, Alison Coogan, Andrea Madrigrano, Cristina O’Donoghue. Targeted Axillary Lymph Node Dissections Using Radar Reflector Localization Can Reduce Unnecessary Axillary Lymph Node Dissections in Node Positive Patients Treated with Neoadjuvant Chemotherapy [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 P2-14-19.

Abstract P2-03-21: Chemotherapy is not mandatory in premenopausal, node-positive, HR+HER2- breast cancer patients

Abstract Background: The RxPONDER trial demonstrated that chemotherapy improves survival in premenopausal, node-positive, HR+HER2- breast cancer patients irrelative of genomic risk. However, the rate of ovarian function suppression (OFS) was under 20%, questioning whether hormone therapy with OFS would be sufficient in genomic low risk patients. The survival outcome of premenopausal, node-positive, HR+HER2- breast cancer patients were retrospectively reviewed, to investigate the non-inferiority of only hormone therapy with OFS in this population. We also retrospectively reviewed patients who underwent genomic multigene assay in this population. Patients and methods: Breast cancer patients who underwent primary surgery between 1990 – 2013 at Asan Medical Center were retrospectively reviewed in this study. Patients who were 50 years old or younger, HR+HER2- breast cancer and T2/3N0 or T1/2N0 were included. Premenopausal patients who underwent the MAMMAPRINT® test between January 2018 – April 2021 were also reviewed and analyzed. Recurrence was defined as locoregional recur and distant metastasis. Disease-free survival (DFS) and distant metastasis-free survival (DMFS) was analyzed using the Kaplan-Meier survival analysis and log-rank test. Results: A total of 6,220 patients who were 50 years or younger underwent primary breast cancer surgery for HR+HER2- breast cancer between 1990 – 2013. Among them, 762 patients were T2/3N0 and 1,283 patients were T1/2N0. Most of the patients (N=1,652, 80.8%) underwent chemotherapy. Among patients who only had hormone therapy, 48 (12.2%) patients only had tamoxifen and 345 (87.8%) patients had tamoxifen with OFS (TAM+OFS). The median follow-up was 107 months. The 8-year DFS was 87.2% in the chemotherapy group, compared to 90.2% in the TAM+OFS group (log-rank test p-value 0.499). The 8-year DFMS had no significant difference also between the chemotherapy and TAM+OFS group also (90.7% vs. 93.5% retrospectively, log-rank test p-value 0.184). DFS and DMFS did not differ in the subgroup analysis of T2/3N0 and T1/2N0 too. A total of 270 premenopausal patients underwent the MAMMAPRINT® test for HR+HER2-, N1 breast cancer between Jan 2018 – April 2021. Among them, 136 (50.4%) patients had low genomic risk and 134 (49.6%) had high genomic risk. Among the low genomic risk patients, 17 (19.9%) patients had only tamoxifen, 107 (78.7%) had TAM+OFS and 1 (0.7%) patient had aromatase inhibitor. The median follow-up period was 26 months. There were seven recurrence events, 2 distant metastasis and 5 locoregional recurrences. Among the low genomic risk patients, 1 patient had lung metastasis and 1 patient had local recurrence. Both patients had only TAM+OFS. Conclusion: In this study, TAM+OFS showed no significant survival difference compared to chemotherapy in premenopausal, HR+HER2- patients. Patient selection is essential to omit chemotherapy in this population. The predictive value of genomic multigene assay for chemotherapy in premenopausal, HR+HER2-, node positive patients warrant further evaluation. Several clinical trials are being prepared to answer this question. Citation Format: Tae-Kyung Yoo, Sae Byul Lee, Youngwon Lee, Yunghyun Hwang, Eunju Shin, Jin Lee, Hee Jeong Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son. Chemotherapy is not mandatory in premenopausal, node-positive, HR+HER2- breast cancer patients [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 P2-03-21.

Abstract P5-01-05: A Predictive Model for Axillary Pathologic Response after Neoadjuvant Chemotherapy for Clinically Node-Positive Breast Cancer

Abstract Purpose: Neoadjuvant chemotherapy (NAC) has resulted in the eradication of axillary lymph node metastasis in approximately 40% of patients. Sentinel lymph node biopsy (SLNB) could be an alternative surgical procedure for these patients to avoid complications from axillary lymph node dissection (ALND). However, high false-negative rates of SLNB for clinically node-positive patients were reported in previous prospective trials. The aim of the present study was to evaluate clinicopathological factors and imaging characteristics by MRI and ultrasound (US) as predictors of axillary pathologic complete response (ypN0) after NAC, which enables to identify candidates for SLNB in patients with clinically node-positive disease. Patients and methods: We identified 177 patients with clinically node-positive breast cancer who received NAC from May 2009 to May 2021. All patients underwent MRI and US before and after NAC. Patients were judged to be node-positive when they have the cytologically-proven nodal disease by fine-needle aspiration (FNA) or suspicious lymph nodes by diagnostic imaging. Lymph nodes with the cortical thickness (&amp;gt;3.5mm), loss of fatty hilum, or round shape (short-axis/long-axis ratio &amp;gt; 0.5) were defined as suspicious lymph nodes. To develop a predictive model for ypN0, the association between ypN0 status and clinicopathological and imaging characteristics was assessed by multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was used to evaluate discrimination by the model. The model was further evaluated in the validation cohort with 20 patients who received NAC from March 2021 to December 2021. Results: The median age was 54.0 (range: 22-79) years and the mean tumor size was 3.97 ±2.29cm. Of 177 patients, 90 (50.8%) patients had luminal, 47 (26.6%) had HER2-positive, and 40 (22.6%) had triple-negative disease. Sequential anthracycline and taxane were administered for 157 (88.7%) patients, and 45 (95.7%) patients with HER2-positive-disease received concomitant anti-HER2 agents preoperatively. Overall, 77 (43.5%) patients achieved ypN0. Independent predictors of ypN0 status were clinical stage N1 (odds ratio [OR]: 9.17 vs. cN2-3, p=0.002), absence of lymphadenopathy after NAC (OR: 8.54, p&amp;lt; 0.001), breast complete response (CR) by MRI (OR: 5.96, p&amp;lt; 0.001), HER2 positivity (OR: 3.80, p=0.008), nuclear grade (NG) 3 (OR: 2.77 vs. NG1-2, P=0.020) and hormone receptor negativity (OR: 2.52, p=0.048). In a model using these predictors, the area under the ROC curve was 0.887 (95% confidence interval: 0.839-0.935, p&amp;lt; 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the model were 80.0%, 82.8%, 77.9% and 84.5%, respectively. In the validation cohort, the sensitivity, specificity, positive predictive value and negative predictive value were 66.7%, 90.9%, 85.7% and 76.9%, respectively. Among 84 patients who were predicted ypN0 by the model, SLNB was performed in 42 (50.0%) patients, and the identification rate of SLN was 95.2% (40/42). Overall, ALND was omitted in 38 (45.2%) patients and irradiation to regional lymph nodes was performed in 23 (60.5%) out of 38 patients. After a median follow-up of 53.9 months, 5-year recurrence-free survival was comparable between patients with or without ALND (78.0% vs. 94.4%, p=0.259). Conclusions: Our predictive model based on clinicopathological factors and imaging characteristics by MRI and US could help to identify good candidates for the omission of ALND after NAC in patients with clinically node-positive breast cancer. Citation Format: Akiko Matsumoto, Saki Naruse, Yuka Isono, Yuka Maeda, Ayana Sato, Miki Yamada, Tatsuhiko Ikeda, Hiromitsu Jinno. A Predictive Model for Axillary Pathologic Response after Neoadjuvant Chemotherapy for Clinically Node-Positive Breast Cancer [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 P5-01-05.

Survival Benefit of Surgical Treatment for Elderly Patients with Intrahepatic Cholangiocarcinoma: A Retrospective Cohort Study in the SEER Database by Propensity Score Matching Analysis.

Despite a rising trend in intrahepatic cholangiocarcinoma (ICC) incidence in the elderly population worldwide, the benefit of surgery for those patients is still controversial. Data from 811 elderly patients diagnosed with non-metastatic ICC were obtained from the US surveillance, epidemiology, and end results (SEER) program database. Propensity score matched (PSM) was conducted for the better balance of baseline. The associations between tumor characteristics and surgery with overall survival (OS) and cancer specific survival (CSS) were estimated using hazard ratios (HR) and 95% confidence intervals (CI). The results showed that ICC patients above 60 years old taking surgery had better OS (hazard ratio [HR], 0.258; 95% CI, 0.205-0.324) and CSS (hazard ratio [HR], 0.239; 95% CI, 0.188-0.303) than patients without surgery. Similar trends in patients above 65 years old, above 70 years old, above 75 years old, and above 80 years old were observed, separately. This benefit was also showed in lymph node-negative (N0) and lymph node-positive (N1) subgroups and N0 patients are more likely to take an advantage from surgery than N1 patients. The different outcomes between surgery and non-surgery suggest that surgical treatment may be recommended for elderly ICC if the tumor is resectable to ensure optimal treatment.

Predictor Factors for the Detection of Positive Nodes in Patients Undergoing Radical Prostatectomy and Lymph Node Dissection

Background: The detection of positive lymph nodes after a lymph node dissection changes the clinical prognosis; therefore, we evaluated what factors help us predict the presence of positive lymph nodes. Methods: A retrospective analysis of all radical prostatectomies and extended lymph node dissection performed from January 2010 to October 2018 in our centre was conducted. The variables included in the Briganti nomogram (preoperative PSA, Gleason biopsy, percentage of cores, and clinical stage) were considered, as well as perineural invasion and involvement of the seminal vesicles in the prostate biopsy; Results: A total of 110 lymph node dissections are obtained. Patient mean age is 64.18 years (46.55–75.91). Of the 110 lymphadenectomies performed, 16 patients (14.5%) presented positive nodes. Presenting infiltrated seminal vesicles, perineural invasion, higher PSA, higher clinical stage, higher Gleason biopsy and percentage of cores is more likely to have statistically significant lymph node involvement (p &lt; 0.05). In the multivariate analysis, the percentage of positive core, together with the involvement of the seminal vesicles and Gleason ≥ 4 in the majority are predictor factors for positive nodes (p &lt; 0.01); Conclusions: The percentage of positive cores, the involvement of the seminal vesicles, and the majority Gleason ≥ 4 are independent predictors of lymph node involvement in prostate cancer.

Adjuvant Chemotherapy De-Escalation with Genomic Assay Protocol in Patients with Early Breast Cancer: A Single-Centre Prospective Cohort Study.

Genomic assays are useful tools for tailoring adjuvant treatment in early breast cancer. We aimed to analyse the role of an institutional protocol of a genomic assay for chemotherapy de-escalation. Prospective cohort study of all consecutive women diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-negative early breast cancer, tested with the 21-gene Recurrence Score (RS) assay from August 2015 to July 2018 at a Portuguese cancer centre. For being tested, patients should meet at least one of the pre-defined inclusion criteria: i) luminal A-like, pT2pN0; ii) luminal A-like, 1 - 3 positive nodes and comorbidities with higher risk of chemotherapy-induced toxicity; iii) pT1-2pN0, progesterone receptor ≤ 20% and/or Ki67 14% - 40%. Adjuvant treatment was de-escalated to isolated endocrine therapy if RS was less than 18. We measured the reduction in chemotherapy prescribing and its clinical impact, the RS association with pathologic features, and the protocol feasibility. We tested 154 women with a median age of 61 years old (range: 25 - 79), 69% postmenopausal. Tumours were mainly pT1 (55%), pN0 (82%), invasive ductal (73%), G2 (86%), luminal B-like (69%) and stage IA (85%). We obtained a RS less than 18 in 60% of women, with an overall adjuvant chemotherapy reduction of 65%. Seven (95% confidence interval: 5 - 10) patients needed to be screened with the 21-gene RS assay to prevent one clinically relevant adverse event during the first six months of adjuvant treatment. Considering the currently used RS cut-off, only 9% of node-negative and 11% of node-positive patients had RS over 25. We found no relevant associations between RS and pathologic features. The protocol was feasible and did not compromise the adequate timing for adjuvant treatment. These criteria allowed the de-escalation of adjuvant systemic treatment in at least six out of ten women.

Defining the optimal target-to-background count rate to identify positive lymph nodes in patients undergoing robot-assisted 99mtc-PSMA-radioguided surgery for prostate cancer: A per-region analysis of a prospective, phase II study

Defining the optimal target-to-background count rate to identify positive lymph nodes in patients undergoing robot-assisted 99mtc-PSMA-radioguided surgery for prostate cancer: A per-region analysis of a prospective, phase II study

Outcomes and bioethical implications of lymphadenectomy in mastectomized patients: Importance and indication of ultrasound-guided fine-needle aspiration biopsy

Lymph node involvement is the main prognostic factor in breast cancer. Mastectomized patients usually undergo lymphadenectomy (LA) of micrometastatic sentinel lymph nodes (SLNs) despite the evidence of AMAROS trial to replace this therapy with radiotherapy in select cases. We demonstrate the ability of ultrasonography to detect non-metastatic or micrometastatic SLNs. Method: 132 patients who underwent mastectomy were evaluated. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was indicated for suspicious lymph nodes. LA and SNL biopsy (SLNB) were performed in patients with positive and negative FNAB, respectively. LA was performed in cases of positive FNAB or positive SLNB except in the presence of isolated tumor cells and micrometastatic SLNs. The tumor burden after LA in patients with negative FNAB and positive SLNB was measured, and the presence of two or fewer positive SLNs was considered a low burden. Results: Sensitivity of FNAB for detecting positive lymph nodes in patients with a high tumor burden was 93% in our series, specificity was 84%. Positive (PPV) and negative predictive value (NPV) were respectively 60% and 79%. Conclusions: LA could have been avoided in 90% of mastectomized patients with negative FNAB and a low tumor burden who met the AMAROS criteria with a high NPV (79%).