Number Of Positive Axillary Lymph Nodes Research Articles

Development and validation of a nomogram for predicting internal mammary sentinel node metastasis in breast cancer patients

ObjectiveInternal mammary nodes are important in breast cancer prognosis, but their diagnosis is often missed in clinical practice, leading to inaccurate staging and treatment. We developed a validated nomogram to predict the presence of internal mammary sentinel nodes (IMSN) metastasis. MethodsA total of 864 sequential IMSN biopsy procedures from a prospective studies database of 1505 cases were used for model development and validation. Multivariable logistic regression was performed on 519 sequential IMSN biopsy procedures from multi-center data between August 2018 and July 2022 to predict the presence of IMSN metastasis. A nomogram was developed based on the logistic regression model and subsequently applied to 345 sequential IMSN biopsy procedures from single-center data between November 2011 and July 2018. The model's discrimination was assessed using the area under the receiver operating characteristic curve. ResultsThe overall frequency of IMSN metastasis was 17.0% in our study. A predictive model for IMSN metastasis was constructed using tumor size, tumor location, lymphovascular invasion, the number of positive axillary nodes (P < 0.05 for all variables in multivariate analysis), and histological grade (P < 0.05 only in univariate analysis). The nomogram was accurate, with a concordance index of 0.84 in the bootstrapping analysis and an area under the receiver operating characteristic curve of 0.80 in the validation population. ConclusionOur nomogram provides an accurate and validated multivariable predictive model for estimating the individual likelihood of having IMSN metastasis. This may be useful for personalized treatment decisions regarding internal mammary radiotherapy in breast cancer patients.

Abstract P2-14-06: Prospective, multicenter, clinical validation study of the repeatability and accuracy of internal mammary sentinel lymph node biopsy with modified injection technique (CBCSG026/CBCSG027)

Abstract Background: As a first-echelon nodal drainage site of breast cancer, the status of axillary lymph nodes (ALN) and internal mammary lymph nodes (IMLN) is both valuable for regional staging and treatment choice. The internal mammary sentinel lymph node biopsy (IM-SLNB) may provide minimally invasive staging, and guide individual IMLN radiation. Modified technique (periareolar intraparenchymal, high volume and ultrasound guidance) got a high internal mammary sentinel lymph nodes (IM-SLN) visualization rate of 71.1% in single center, and the prospective multicenter study was designed to verify its repeatability (CBCSG026, NCT03541278). High visualization rate and low false negative rate are prerequisites for the widespread of IM-SLNB. The question arises as to whether IM-SLN detected with the modified technique should be considered as “true” IM-SLN. The prospective, multicenter, clinical validation study of IM-SLNB followed by internal mammary lymph node dissection (IM-LND) was designed to verify the accuracy of IM-SLNB in patients with ALN positive breast cancer (CBCSG027, NCT03024463). Methods: While CBCSG026 trial enrolled patients with both axillary negative and positive breast cancer, CBCSG027 trial only enrolled axillary positive patients receiving mastectomy (either biopsy proving cN+ disease or cN0 with positive axillary SLN). The 1st to 3rd intercostal IM-LND was performed immediately after IM-SLNB to verify its accuracy in the CBCSG027 trial. Result: From May 2018 to June 2022, 600 and 264 patients were enrolled in the CBCSG026 and CBCSG027 trial from seven centers in China, respectively. Among the 600 recruited patients in the CBCSG026, the IM-SLN visualization rate was 65.0% (390/600), which was significantly related to patient’s age, body mass index, radiotracer intensity and interval time between injection and IM-SLN identification (all P&amp;lt; 0.05). The IM-SLNB successful rate was 97.4% (380/390), and the complication was 6.9%. The median number of IM-SLN was 1. The overall IM-SLN metastases rate was 18.9% (72/380), with 33.0% (65/195) and 3.8% (7/185) in ALN positive and negative patients, respectively. Multivariate analysis showed that the tumor size (P=0.028), the tumor location (P&amp;lt; 0.001) and the number of positive ALNs (P&amp;lt; 0.001) were independent predictors of IM-SLN metastasis. Those variables were included in a novel nomogram (Table 1), which was significantly better than the probability based on the number of metastatic ALNs alone according to the current guidelines (area under the curve: 0.860 vs. 0.804, P&amp;lt; 0.001). Of the 264 patients enrolled in the CBCSG027 trial, 185 patients (70.1%) had IM-SLN visualization (included 107 with cN+ disease and 78 with positive axillary SLN). The median number of IM-SLN and IM-nSLN was 2 (1~4) and 3 (1~9), respectively. The positive rate of IMLN and IM-SLN was 37.8% (70/185) and 36.8% (68/185), respectively, yielding the false negative rate of IM-SLNB 2.9% (2/70), the accuracy of 98.9% (183/185) and the sensitivity of 97.1% (68/70). The false negative rate of patients with cN+ disease and patients with positive axillary SLN was 4.8% (2/42) and 0, respectively. The positive IM-SLNs were the only positive IMLNs identified in 51.4% (36/70) patients. IM-SLNB can change the pN stages of 37.2% (68/183) patients. IMLN irradiation could be avoided in 72.7% (80/110) patients with axillary pN1 and 46.7% (35/75) with pN2/N3 disease in the study. Conclusions: The modified technique of radiotracer injection (periareolar intraparenchymal, high volume, and ultrasound guidance) can significantly improve the detection rate of IM-SLN with very low false-negative rate with the prospective, multicenter validation results, providing minimally invasive staging and guiding individual IMLN radiation. When there is no IM-SLN visualization, the nomogram can predict the risk of IMLN metastasis and guide IMLN radiation. The nomogram which can predict the risk of IMLN metastasis The nomogram which can predict the risk of IMLN metastasis Citation Format: Yong-Sheng Wang, Qing Lu, Shi-Guang Zhu, Wen-He Zhao, Guang-Lun Yang, Yuan-Xi Huang, Hong Zhong, Xiao Sun, Pengfei Qiu. Prospective, multicenter, clinical validation study of the repeatability and accuracy of internal mammary sentinel lymph node biopsy with modified injection technique (CBCSG026/CBCSG027) [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 P2-14-06.

Clinical, Histopathologic Features and Outcome of Breast Cancer in UK Women of Ethnic Origin.

Objective:Breast cancer (BC) in non-Caucasian females is understudied and its management is based on Caucasian data. 30 % of the West Midlands females are non-Caucasian. We aimed to elucidate the pathologic features, molecular profile, and outcome of non-Caucasian breast cancer. Methods:Breast cancers (BCs) of different ethnic origins diagnosed at a large Birmingham tertiary referral hospital between 2000 and 2016 were identified. Detailed clinical and histological data were collected and statistically analyzed. Results:Out of 7554 BC cases, 749 were of ethnic ancestry and median age of 51 years. These comprised 47 in-situ and 702 invasive carcinomas of presenting symptomatically in 86.2% of patients. 53.4% of the invasive carcinomas measured >20 mm. Cancers were predominantly of grade 3 (45%), and grade 2 (42.4%). Median NPI was 4.35. 65.1% of the ethnic carcinomas were of luminal subtype, 18.6% were Her2 positive and 16.2% triple-negative. Median overall survival was 62 months. Five and ten-year survival was 81.7% & 68.4% respectively. Ethnicity correlated with higher NPI (p <0.001), larger tumour size (p= 0.001) and larger number of positive axillary nodes (p=0.007). Negative correlations were found between age at diagnosis and both invasive tumour size & grade (p< 0.001) and between tumour grade and overall survival (p= 0.006). Conclusion:Compared with Caucasian breast cancer, non-Caucasian tumours presented predominantly symptomatically at younger age, were of larger size, higher grade with more unfavorable phenotypes and shorter survival. This is important in counselling, planning management and follow up of non-Caucasian patients.

POstmastectomy radioThErapy in Node-posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a study protocol for a multicenter prospective phase III randomized controlled trial

BackgroundVarious randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques.MethodsPOTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1–3 vs. 4–9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed.DiscussionThis trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy.Trial registrationClinicalTrails.gov, NCT04320979. Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979

Lipofilling after Breast Conserving Surgery: A Comprehensive Literature Review Investigating Its Oncologic Safety

Lipofilling has regenerative properties used to improve deformities after breast conserving surgery. Our hypothesis is that there is inadequate data to ensure that lipofilling does not increase locoregional cancer recurrence after breast conserving surgery. A PRISMA comprehensive literature review was conducted of articles published prior to October 2019 investigating recurrence in patients who underwent lipofilling after breast conserving surgery. All forms of breast conserving surgery, fat grafting, and injection intervals were included. Patients undergoing mastectomy were excluded. Requirements to define lipofilling as safe included (I) a defined interval between resection and lipofilling; (II) a minimum follow-up period of 6 years from tumor resection; (III) a minimum follow-up period of 3 years from lipofilling; (IV) presence of a control group; (V) controls matched for ER/PR/Her-2; (VI) a sub-group analysis focusing on ER/PR/Her-2; (VII) adequate powering. Nineteen studies met inclusion criteria. The range in time from breast conserving surgery to fat injection was 0-76 months. The average time to follow-up after lipofilling was 23 days-60 months. Two studies had a sufficient follow-up time from both primary resection and from lipofilling. Seventeen of the nineteen studies specified the interval between resection and lipofilling, but there is currently no consensus regarding how soon lipofilling can be performed following BCS. Eight studies performed a subgroup analysis in cases of recurrence and found recurrence after lipofilling was associated with number of positive axillary nodes, intraepithelial neoplasia, high grade histology, Luminal A subtype, age <50, Ki-67 expression, and lipofilling within 3 months of primary resection. Of the eleven studies that included a comparison group, one matched patient for Her-2 and there was a statistically significant difference in Her-2 positive cancers in the study arms of two articles. Several studies deemed lipofilling safe, two showed association of lipofilling and local recurrence, and most studies concluded that further research was needed. Insufficient and contradictory data exists to demonstrate the safety of lipofilling after breast conserving surgery. A multicentered, well designed study is needed to verify the safety of this practice.

Lipofilling after breast conserving surgery: a comprehensive literature review investigating its oncologic safety.

Lipofilling has regenerative properties used to improve deformities after breast conserving surgery. Our hypothesis is that there is inadequate data to ensure that lipofilling does not increase locoregional cancer recurrence after breast conserving surgery. A PRISMA comprehensive literature review was conducted of articles published prior to October 2019 investigating recurrence in patients who underwent lipofilling after breast conserving surgery. All forms of breast conserving surgery, fat grafting, and injection intervals were included. Patients undergoing mastectomy were excluded. Requirements to define lipofilling as "safe" included (I) a defined interval between resection and lipofilling; (II) a minimum follow-up period of 6 years from tumor resection; (III) a minimum follow-up period of 3 years from lipofilling; (IV) presence of a control group; (V) controls matched for ER/PR/Her-2; (VI) a sub-group analysis focusing on ER/PR/Her-2; (VII) adequate powering. Nineteen studies met inclusion criteria. The range in time from breast conserving surgery to fat injection was 0-76 months. The average time to follow-up after lipofilling was 23 days-60 months. Two studies had a sufficient follow-up time from both primary resection and from lipofilling. Seventeen of the nineteen studies specified the interval between resection and lipofilling, but there is currently no consensus regarding how soon lipofilling can be performed following BCS. Eight studies performed a subgroup analysis in cases of recurrence and found recurrence after lipofilling was associated with number of positive axillary nodes, intraepithelial neoplasia, high grade histology, Luminal A subtype, age <50, Ki-67 expression, and lipofilling within 3 months of primary resection. Of the eleven studies that included a comparison group, one matched patient for Her-2 and there was a statistically significant difference in Her-2 positive cancers in the study arms of two articles. Several studies deemed lipofilling "safe," two showed association of lipofilling and local recurrence, and most studies concluded that further research was needed. Insufficient and contradictory data exists to demonstrate the safety of lipofilling after breast conserving surgery. A multicentered, well designed study is needed to verify the safety of this practice.

Discussion on the indications of internal mammary sentinel lymph node biopsy in breast cancer in the era of precision medicine

Objective: To determine the clinical benefits of internal mammary sentinel lymph node biopsy (IM-SLNB) acquired by breast cancer patients with clinically positive axillary lymph node (ALN), and further optimize the IM-SLNB indications. Methods: All primary breast cancer patients with clinically positive ALN from February 2014 to September 2017 were prospectively recruited in this study. IM-SLNB was performed under the guidance of the modified injection technique. The success rate and visualization rate of IM-SLNB, metastatic rate of internal mammary sentinel lymph node (IMSLN) and its related factors were analyzed, and the clinical benefits were accessed according to the current guidelines. Results: Among 126 patients, all of 94 patients (74.6%) who showed internal mammary drainage successfully underwent IM-SLNB. The incidence of internal mammary artery bleeding and pleural lesion were 4.3%(4/94) and 9.6%(9/94), respectively. The metastatic rate of IMSLN was 38.3% (36/94), which was significantly associated with the number of positive ALN (P<0.001) and tumor size (P=0.024). The lymph node staging of 94 patients who underwent IM-SLNB was more accurate. Among them, 36 cases with positive IMSLN underwent internal mammary radiotherapy (IMRT), while the other 58 cases with negative IMSLN avoided radiotherapy. Conclusions: IM-SLNB should be routinely performed in patients with positive ALN. IM-SLNB can provide more accurate staging and guide tailored IMRT to benefit more breast cancer patients.

Higher axillary lymph node metastasis burden in breast cancer patients with positive preoperative node biopsy: may not be appropriate to receive sentinel lymph node biopsy in the post-ACOSOG Z0011 trial era

BackgroundBreast cancer patients with suspicious axillary lymph node (ALN) at ultrasound and positive fine-needle aspiration (FNA) results were required to receive ALN dissection (ALND), which was not certain in the post-ACOSOG Z0011 era. We aim to evaluate the ALN metastasis burden in these patients, thus to illustrate whether they can follow the ACOSOG Z0011 trial procedure.MethodsClinically, T1–2 N0 breast cancer patients with positive preoperative ALN biopsy (FNA group) or 1–2 positive sentinel nodes (SLNB group) were retrospectively analyzed. ALN metastasis burden was compared between the two groups, which were further analyzed in certain subtypes. An association between clinicopathological factors and ≥ 3 ALN metastasis was also analyzed.ResultsA total of 388 patients were included: 202 in the FNA group and 186 in the SLNB group. The FNA group had a significantly higher number of positive ALN (5.18 vs. 1.77, P < 0.001) and a larger proportion of patients with ≥ 3 ALN metastasis (58.42% vs. 11.83%, P < 0.001) than the SLNB group, which was not influenced by different tumor size stage and molecular subtypes. ALN metastasis identified by FNA was independently associated with a high rate of ≥ 3 ALN metastasis (OR = 6.98, 95% CI 1.95–25.02, P = 0.003).ConclusionsPatients with positive preoperative ALN biopsy had a higher ALN metastasis burden than patients with 1–2 positive SLNs, which was also the strongest factor associated with ≥ 3 ALN metastasis, indicating that these patients are not appropriate to receive SLNB in the post-ACOSOG Z0011 trial era.

Abstract 675: Analysis of post mastectomy radiation outcomes in breast cancer patients with 1-3 positive axillary lymph nodes : A review of the National Cancer Database

Abstract Background: The benefit of Post mastectomy radiation (PMRT) has been confirmed in breast cancer patients with ≥4 positive axillary lymph nodes (PALN). The role of PMRT in patients with 1-3 PALN is not well defined. Methods: We identified 102,103 breast cancer patients with mastectomy and 1-3 PALN registered to the National Cancer Database (NCDB) between 2004- 2012. Primary outcome was overall survival. Adjusted variables include age, race, comorbidity, insurance, income, education, distance travelled, diagnosing/treating facility, treatment delays, hormone receptor status, regional lymph nodes, stage and treatment modalities. 8 treatment modalities were defined: +/- radiation, +/- adjuvant chemotherapy, +/- adjuvant hormone therapy. Univariate and multivariate analyses were performed to identify factors that predict overall survival. Results: Patients with 1, 2, and 3 PALN comprised 55.7%, 27.6% and 16.6% of the population, respectively. 58.4% of patients received radiation. Younger age (&amp;lt;50years), Asian race, private insurance, annual income &amp;gt;$46,000, lower AJCC tumor stage, hormone receptor positive status and lower number of PALN were independently associated with a lower risk of death in multivariate analysis. Compared to patients who did not receive additional therapy, radiation alone was associated with a non-significant increased risk of death HR 1.10 (95% CI [0.92-1.31]). The addition of hormone and chemotherapy significantly reduced the risk of death HR 0.36 (95% CI [0.33- 0.3]). Stratified by regional lymph nodes, patients with 1 or 2 PALN had a trend towards increased risk of death with radiation alone compared to patients who did not receive radiation, hormone or chemotherapy. In patients with 3 PALN, there was a trend towards reduced mortality with radiation alone HR 0.89 (95% CI [0.63- 1.23]). Conclusions: To our knowledge this retrospective study is the largest such review of the outcomes of breast cancer patients with 1-3 PALN receiving adjuvant radiation following mastectomy. Our study found no measurable reduction in risk of death for those patients who received radiation therapy compared to those who did not. We also note that, with an increasing number of PALN, patients receiving PMRT either alone, or with chemotherapy or hormonal therapy, appeared to have a decrease in the risk of death compared to the populations that had not received PMRT. Based on this analysis, the routine addition of radiation following mastectomy is not indicated in patients with 1-3 PALN. The addition of adjuvant hormone and/or chemotherapy was associated with a significant survival advantage. Citation Format: Anu Paul, Runhua Shi, Prakash Peddi, Gary Burton. Analysis of post mastectomy radiation outcomes in breast cancer patients with 1-3 positive axillary lymph nodes : A review of the National Cancer Database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 675.

The relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among elderly women with incident breast cancer.

To examine the relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among a population-based cohort of elderly women with incident breast cancer, with a special focus on identifying sources of socioeconomic (SES) disparities in outcomes. We identified women with newly diagnosed breast cancer in 2006-2009 from the Surveillance and Epidemiology End Result study linked with Medicare claims. A Classification and Regression Tree (CART) model was applied to 13 individual indicators of neoadjuvant and adjuvant breast cancer treatment, tumor characteristics, and patient sociodemographic variables to identify patterns with the greatest discriminant value in predicting 5-year survival. We subsequently examined the extent to which these patterns varied by the patient's SES. Survival probabilities associated with the 18 unique CART-identified patterns ranged from 22 to 87%. The number of positive axillary nodes was the best single discriminator between high and lower survival outcomes. The most common discriminant factor among patterns with poor (< 25%) survival was the absence of radiation treatment, followed by the presence of comorbidities, tumor size > 2cm, and no breast surgery. Relative to high SES women, poor women were nearly four times (12.3% vs. 3.2%, p < 0.001) as likely to be classified in the pattern associated with worse survival, and less likely (31.7% vs. 52.9%, p = 0.04) to receive the pattern associated with the greatest survival. Greater adoption of effective patterns of care could improve survival of elderly women with incident breast cancer overall, and reduce SES disparities therein.

Internal Mammary Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer.

PurposeThe definition of nodal pathologic complete response (pCR) after a neoadjuvant chemotherapy (NAC) just included the evaluation of axillary lymph node (ALN) without internal mammary lymph node. This study aimed to evaluate the feasibility of internal mammary-sentinel lymph node biopsy (IM-SLNB) in patients with breast cancer who underwent NAC.MethodsFrom November 2011 to 2017, 179 patients with primary breast cancer who underwent operation after NAC were included in this study. All patients received radiotracer injection with modified injection technology. IM-SLNB would be performed on patients with internal mammary sentinel lymph node (IMSLN) visualization.ResultsAmong the 158 patients with cN+ disease, the rate of nodal pCR was 36.1% (57/158). Among the 179 patients, the visualization rate of IMSLN was 31.8% (57/179) and was 12.3% (7/57) and 87.7% (50/57) among those with cN0 and cN+ disease, respectively. Furthermore, the detection rate of IMSLN was 31.3% (56/179). The success rate of IM-SLNB was 98.2% (56/57). The IMSLN metastasis rate was 7.1% (4/56), and all of them were accompanied by ALN metastasis. The number of positive ALNs in patients with IMSLN metastasis was 3, 6, 8, and 9. The pathology nodal stage had been changed from pN1/pN2 to pN3b. The pathology stage had been changed from IIA/IIIA to IIIC.ConclusionPatients with visualization of IMSLN should perform IM-SLNB after NAC, especially for patients with cN+ disease, in order to complete lymph nodal staging. IM-SLNB could further improve the definition of nodal pCR and guide the internal mammary node irradiation.

Abstract CT109: Adjuvant ovarian suppression in high risk premenopausal breast cancer: ten-year follow-up of a phase I-II study

Abstract Background: Two randomized studies have shown the benefit of ovarian suppression in the adjuvant treatment of high risk premenopausal breast cancer, both with estrogen receptor positive (ER+) (Pagani et al. N Engl J Med 2014) and estrogen receptor negative (ER-) (Moore et al. N Engl J Med 2015). Nevertheless the median follow-up of these studies was limited to 68 and 49 months, respectively. Here we present the results of a large, phase I-II study, of adjuvant ovarian suppression in ER+ and in ER- patients, after a median follow-up of 123 months (range 93-223). Two hundred patients were enrolled between 06-1997 and 06-2007. The primary end point of the study was to find the best dose and schedule of a luteinizing hormone releasing hormone (LH-RH) analogue given to prevent ovarian failure in premenopausal patients treated with adjuvant chemotherapy. Secondary end points were disease free survival (DFS) and overall survival (OS). Methods: One week before chemotherapy, a LH-RH analogue was administered, 3.75 mg every 28 days for 1 year to the first cohort of 64 patients. The same monthly dose was given, for 2 years, to the second cohort of 36 patients. Because we had observed a decrease of 31% in the recurrence rate for the longer administration of LH-RH analogue, the 11.25 mg dose every 84 days, for 5 years, was chosen for the remaining 100 patients. The treatment consisted of: a- LH-RH analogue; b- Breast conserving (74%) and radical surgery (26%); c- Tailored systemic therapy concurrent with radiation therapy; d- Aromatase inhibitor in ER+ patients. Results: The median age was 43 years (range 26-45), the mean number of positive axillary nodes was 3.2 (range 1-25), including 20 patients with &amp;gt;10 positive nodes. 71% of patients were ER+ and/or progesterone receptor positive (PGR+), 29% were ER - and PGR-, 21% of patients were c-ErbB-2 positive. The median KI-67 was 30% (range 15% -100%). Ovarian failure rate was 10% in patients younger than 40 years and 44% in patients older than 40 years. The 15-year DFS and OS rate were 64% and 73%, respectively. 15-year DFS rate of ER+ and ER- patients were 74% and 44% respectively (P&amp;lt;0.005), while the 15-year OS rate were 74% and 75%, respectively (P&amp;gt;0.005). The usual pattern of toxicity of chemotherapy was observed. Hot flashes and G1 osteopenia occurring after LH-RH analogue administration were temporary and receded after the cessation of therapy. Conclusions: LH-RH administration, concurrent with chemotherapy is tolerable and useful. Five full term pregnancies were observed. The long-term recurrence and survival rate for ER+ and ER-patients were similar, with different patterns: ER+ patients had disease recurrences even after 13 years, while ER- patients had late new primaries, but no recurrence after 5 years. Citation Format: Francesco Recchia, Giampiero Candeloro, Massimo Bratta, Michele Rosselli, Silvio Rea. Adjuvant ovarian suppression in high risk premenopausal breast cancer: ten-year follow-up of a phase I-II study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT109.

Abstract P5-15-06: 10-year follow-up of adjuvant ovarian suppression in high risk premenopausal breast cancer

Abstract Background: A large randomized study has shown the value of temporary ovarian suppression during the administration of chemotherapy in the treatment of high risk estrogen receptor positive (ER+) breast cancer (BC) (Pagani et al. N Engl J Med 2014). In another study ovarian suppression added to chemotherapy appeared to protect ovarian function (Moore et al. N Engl J Med 2014) and improve the expected outcome of estrogen receptor negative (ER-) BC. Nevertheless, both these studies have a median follow-up time limited to 68 months and 49 months, respectively. Here we present the data of a large non randomized phase II study of adjuvant ovarian suppression in ER+ and ER- breast cancer with a median follow-up of 120 months (range 90-220 months). The primary end point was the ovarian function preservation rate, secondary end points were disease-free survival (DFS) and overall survival (OS). Methods: Between 06-1997 and 06-2007, 200 premenopausal, high risk early BC patients entered the study. All patients received the LH-RH analogue before starting chemotherapy. Breast conserving and radical surgery were performed in 74% and 26% of patients, respectively. Systemic therapy was tailored to the biological characteristics of each patient, and followed by radiation therapy and hormonal therapy in ER+ tumors. Results: The median patient's age was 43 years (range 26-45). The mean number of positive axillary nodes was 3.2 (range 1-25). Seventy-one % of patients were ER+ and/or progesterone receptor positive (PGR+), 29% were ER - and PGR-. The median KI-67 was 30% (range 15% -100%). Twenty-one % of patients were c-ErbB-2 positive. After a median follow up of 120 months (range 90-220), normal menses returned in 90% of patients younger than 40 years and in 56% of patients older than 40 years. The 10 and 15-year DFS rate were 85.5% and 71%, respectively, while the 10 and 15-year OS rate were 91%, and 71%, respectively. The standard pattern of toxicity of chemotherapy was observed. Hot flashes and G1 osteopenia occurring after LH-RH analogue administration were temporary and subsided after the cessation of therapy. Conclusions: LH-RH administration, concurrent with chemotherapy is tolerable and effective. Five full term pregnancies were documented. A favourable impact on the expected DFS and OS was observed. ER- patients had late new primaries, but no recurrence after 5 years, while ER+ patients had disease recurrence even after 13 years. Citation Format: Recchia F, Candeloro G, Rosselli M, Bratta M, Rea S. 10-year follow-up of adjuvant ovarian suppression in high risk premenopausal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-15-06.

Abstract P2-12-15: The role of neck dissection in breast cancer patients with synchronous and metachronous ipsilateral supraclavicular lymph node metastasis

Abstract Purpose: To evaluate the effect of neck dissection in breast cancer patients who present with ipsilateral supraclavicular lymphnode metastasis (ISLM) without distant metastasis and to reveal the outcomes of neck dissection in different molecular subtypes. Methods: A total of 90 patients with synchronous ISLM and 36 patients with metachronous ISLM without distant metastasis between 2000 and 2009 were retrospectively analyzed. Combined-modality treatments were performed, and patients were respectively divided into two parts according to whether they received neck dissection or not. Results: In the synchronous ISLM group, there was no significant difference between the neck dissection and non-dissection group with respect to age, menstrual status, tumour size, and histological type, PR and HER2 status. Patients with negative ER status and a higher number of positive axillary nodes were more common in the neck dissection group. The five-year locoregional relapse free survival (LRFS) was 63.6% in the neck dissection group VS. 48.9% in the non-dissection group, respectively (P=0.359). The 5-year distant metastasis free survival (DMFS) was 37.3% in the neck dissection group VS. 38.5% in the non-dissection group, respectively (P=0.882). Further analyses were performed by the site of metastases. Results showed that the incidence of bone metastasis was lower in neck dissection patients (14.7% vs. 28.6%, P=0.132). Due to the limited amount of patients, subgroup analysis was just performed in the subtypes with negative ER status, negative PR status and negative HER2 status, respectively. The five-year LRFS of patients receiving neck dissection in the subtypes with negative ER status, negative PR status and negative HER2 status was 63.7%, 59.8%and 61.2%, which was much better than their matched non-dissection group, respectively. However, the difference was not statistically significant. The 5-year overall survival (OS) was similar between the neck dissection and non-dissection group in the subtypes of negative ER status and negative PR status, respectively. However, the 5-year OS of HER2 negative subtype significantly decreased in the neck dissection group (37.2% vs. 65.4%, P=0.032). Besides, it's worth mentioning that in the HER2 positive subtype, the mean time to relapse, metastasis and death was shorter in the neck dissection subgroup compared with the non-dissection subgroup. In the metachronous ISLM group, a trend of better regional control, with similar PFS and OS, was achieved in the neck dissection group. Discussion: Neck dissection is an effective approach to improve the regional control for the patients with ISLM, especially for the subtypes with negative ER status, negative PR status and probably positive HER2 status in the synchronous ISLM. But, it might not be comfortable for the patients with negative HER2 status, because of the unfavorable effect on its overall survival. In addition, neck dissection, with better regional control, might be helpful for the control of bone metastasis, which is beneficial for long term survival. Citation Format: Xiao C, Qi X, Chen A, Zhang W, Zhang P, Cao X. The role of neck dissection in breast cancer patients with synchronous and metachronous ipsilateral supraclavicular lymph node metastasis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-15.

HISTOPATHOLOGICAL ANALYSIS AND SURGICAL TREATMENT OF BREAST CANCER--OUR EXPERIENCE.

The aim of this study was to show the descriptive and histopathological analysis and applied surgical technique with early and late post-operative complications in patients with breast cancer who were hospitalized and treated at the General Hospital in Novi Pazar during the period 2009-2011. During the period from 2009 to 2011, 59 patients were operated for breast cancer at the General Hospital in Novi Pazar. The study included the size and type of the tumor, disease stage, surgical techniques and complications, the age of the patients at the moment of surgery and its correlation with the number of metastatic lymph nodes in the axilla and the tumor size, as well as the correlation of the tumor size with the number ofmetastases in the axillary lymph nodes. The dif- ference in the tumor size in relation to the age among the women under 50 and over 50 years of age was not statistically significant (T = -1.203, p > 0.05). There was no statistically significant difference between the number of positive lymph nodes in the women under and over 50 years of age (Mann-Whitney U test, p > 0.05). A significant positive correlation between the tumor size and the number of positive axillary lymph nodes was found (p = 0.308, p < 0.05). A significant positive correlation of the patient's age and breast cancer stage was also confirmed with nonparametric variance analysis by Spearman's Rho (p = 0.337, p < 0.05). The majority of women from this study sample were with Stage II of breast cancer, which points out the necessity for better prevention and education of women in order to improve early diagnosis of breast cancer. The number of positive axillary lymph nodes appears to be an important prognostic factor and a significant positive correlation between the tumor size and the number of positive axillary lymph nodes has been found.

Abstract P2-01-18: Preoperative axillary imaging with ultrasonography: Among the breast cancer patients with lymph node metastases, can we identify the patients who may omit axillary dissection?

Abstract (Introduction) ACOSOG Z11 and EORTC AMAROS showing little benefit to axillary dissection(ALND) for early stage breast cancers with limited nodal disease have led us to questioning the value of preoperative axillary imaging. It may not result in a benefit to the patients to perform ALND by diagnosing a few or small axillary lymph node(ALN) metastases preoperatively. (Aim) A purpose of this study is to determining the association between diagnostic method and metastatic number of ALN metastases, and to find the patients who can omit ALND safely even if with ALN metastases. (Methods)A database of consecutive primary breast cancer patients who underwent comlete ALND at our institution in 2008-2011 was analyzed. After we excluded patients treated with neoadjuvant systemic therapy, a total of 390 patients were included. By diagnostic methods of ALN metastases, we classified them in four groups as follows. Group A (n=41) : suspicious ALNs on axillary ultrasound(AUS) and ultrasound-guided fine needle aspiration cytology (FNAC) positive, Group B (n=47) : only one abnormal ALN on AUS +/- FNAC, Group C(n=53) : multiple abnormanl ALNs +/- FNAC, Group D (n=249) : negative ALNs on AUS but SLNB positive . (Results) The median number (range) of ALN metastases were 3(1-22) in GropuA, 2(0-12) in Group B, 7(1-37) in Group C, 1(1-17) in Group D. There were significant differences in number of metastases between Group A/B/C and Group D (p=.02, p=.01, p=.002). Paitents with 3 or less positive ALNs were 24.5% (13/53) in Group C, whereas 61.0% (25/41) in Group A and 68.1% (32/47) in Group B (p=.04, p=.02). We next evaluated the influence of patient- and tumour-related variables on the number of positive ALNs in Group A/B. Factors such as age, tumour size (&amp;lt;20mm vs &amp;gt;20mm), ER status(positive vs negative), HER2 status (positive vs negative), nuclear grade (1/2 vs 3), menstruation status (pre vs post menopausal) were examined. However there were no significant differences in all factors between the patients with 4 or more ALN metastases and patients with 3 or less ALN metastases. As a result of multivariable analysis, relative risk (95%CI, p-value) of age was 0.92 (0.546-1.347, 0.84), tumour size : 0.82 (0.511-1.418, 0.76), ER status : 1.06 (0.873-1.821, 0.76), HER2 status : 1.17 (0.853-2.390, 0.28), nuclear grade : 0.43 (0.420-1.22, 0.34), menstruation status : 0.85 (0.538-1.693, 0.89). (Conclusion) In our contemporary series, patients diagnosed as ALN metastases preoperatively have significantly more involved nodes compared to SLNB positive patients regardless of the diagnostic method, suggesting that such patients should proceed to ALND. Preoperative axillary imaging are useful to identify node-positive breast cancer patients requiring ALND . Citation Format: Naoto Kondo, Takashi Fujita, Masataka Sawaki, Masaya Hattori, Akiyo Yoshimura, Mari Ichikawa, Junko Ishiguro, Yayoi Adachi, Haruru Kotani, Tomoka Hisada, Hiroji Iwata. Preoperative axillary imaging with ultrasonography: Among the breast cancer patients with lymph node metastases, can we identify the patients who may omit axillary dissection? [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 P2-01-18.

Abstract CT301: Late disease recurrence in estrogen receptor positive (ER+) premenopausal breast cancer (BC)

Abstract Background: BC is often a slowly growing disease. For this reason, in order to establish the validity of a therapeutic approach, we need long term follow up, especially in the adjuvant setting. In addition, estradiol (E2) plays a key role in premenopausal BC growth through the induction of vascular endothelial growth factor (VEGF) and the expansion of T-Regulatory cells (T-Regs). We hypothesized that, decreasing plasma E2, the most important inducer of BC, we could reduce VEGF and, therefore, decrease the recurrence rate in premenopausal patients with high risk breast cancer. After a median follow-up &amp;gt;100 months here we present the results of an adjuvant approach in high-risk premenopausal early breast cancer: Luteinizing hormone releasing hormone (LHRH), tailored chemotherapy, radiation therapy and an aromatase inhibitor in ER+ patients. Primary endpoint of this study was the evaluation of E2 and VEGF; secondary end points were the 5 and 15-year disease-free survival (DFS) and overall survival (OS) rates. Methods: Between June 1997 and June 2007, 200 premenopausal high risk early BC patients were entered into the study. The LH-RH analogue was administered before starting chemotherapy. Breast conserving and radical surgery were performed in 74% and 26% of patients, respectively. Systemic therapy was tailored to the biological characteristics of each patient and followed by radiation therapy and by an aromatase inhibitor to ER+ patients. Results: Median patient's age was 43 years (range 26-45). Mean number of positive axillary nodes was 3.2 (range 1-25). 71% of patients were ER+ and/or progesterone receptor (PGR+), 29% were ER - and PGR-. Median KI-67 was 30% (range 15% -100%). After a median follow-up of 104 months (range 63-180), a statistically significant decrease of E2 (P&amp;lt;0.0001) and VEGF (P&amp;lt;0.0001) were observed. 5-year DFS and OS rate were 89% and 96%, respectively, while the 15-year DFS and OS rate were 62%, and 73%, respectively. ER+ patients had a better DFS (P&amp;lt;0.05) with respect to ER- patients, while no difference was observed in OS. The standard pattern of toxicity of chemotherapy was observed, while hot flashes and G1 osteopenia occurred after LH-RH analogue administration. Conclusions: E2 deprivation with an LH-RH analogue is able to decrease E2 and VEGF and to improve the expected DFS and OS rate in premenopausal high risk ER+ and ER- BC patients, at the price of a moderate toxicity. No recurrence after 5 years was observed in ER- patients who had late new primaries. ER+ patients had recurrences even after 15 years. Long term therapy and new immunologic approaches are being evaluated in premenopausal patients with ER+ tumors. Citation Format: Francesco Recchia, Giampiero Candeloro, Stefano Necozione, Silvio Rea, William Soo Hoo, Tom Cantor. Late disease recurrence in estrogen receptor positive (ER+) premenopausal breast cancer (BC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT301. doi:10.1158/1538-7445.AM2014-CT301

Abstract P6-09-06: Estrogen (E2) suppression following diagnosis of node positive (N+) breast cancer (BC) in premenopause. Long term follow-up of a phase II study

Abstract Background: E2 plays a key role in human reproduction and in premenopausal BC growth through the induction of vascular endothelial growth factor (VEGF) and the expansion of T-Regulatory cells (T-Regs). In addition, few clinical data exist on long-term outcome of high-risk N+ premenopausal BC treated with E2 deprivation, by luteinizing hormone releasing hormone (LH-RH). We hypothesized that E2 suppression, following diagnosis of N+ BC in young premenopausal patients, could decrease VEGF and T-Regs and, therefore, could reduce the recurrence rate. Primary endpoint of this study was the evaluation of T-Regs and VEGF of premenopausal patients with high-risk N+, estrogen receptor positive (ER+) and negative (ER-) early BC, treated with an LH-RH analogue. Secondary endpoints were the 10 and 15-year disease-free survival (DFS) and overall survival (OS) rates. Methods: Between 06-1997 and 06-2007, 200 premenopausal high risk early BC patients were entered into the study. Before starting chemotherapy, the LH-RH analogue was administered, 3.75 mg every 28 days for 1 year to the first 64 patients. The same monthly dose was given, for 2 years, to 36 patients. Having observed a decrease of 31% in the recurrence rate for the longer administration of LH-RH analogue, we gave the 11.25 mg dose every 84 days, for 5 years, to the remaining 100 patients. Breast conserving and radical surgery were performed in 74% and 26% of patients, respectively. Systemic therapy was tailored to the biological characteristics of each patient and followed by radiation therapy, and hormonal therapy in ER+ tumors. Results: Median patient's age was 43 years (range 26-45). Mean number of positive axillary nodes was 3.2 (range 1-25). 71% of patients were ER+ and/or progesterone receptor (PGR+), 29% were ER - and PGR-. Median KI-67 was 30% (range 15% -100%). 21% of patients were c-ErbB-2 positive and 11 of them were treated with trastuzumab for 1 year. After a median follow up of 102 months (range 60-180), a statistically significant decrease of VEGF and T-Regs was observed, both in ER+ (P&amp;lt;0.0001) and ER- patients (P&amp;lt;0.0001). Ten-year DFS and OS rate were 86% and 90%, respectively, while the 15-year DFS and OS rate were 62%, and 73%, respectively. Two c-ErbB-2 positive patients (4.7%), had disease recurrence. ER+ patients had a better DFS (P&amp;lt;0.05) and OS (P&amp;lt;0.0001) with respect to ER- patients. The standard pattern of toxicity of chemotherapy was observed, while hot flashes and G1 osteopenia occurred after LH-RH analogue administration. Conclusions: E2 deprivation with an LH-RH analogue is able to decrease plasma VEGF and T-Regs in premenopausal high risk ER+ and ER- BC patients, at the price of a mild toxicity. A favourable impact on DFS and OS was observed. ER- patients had late new primaries, but no recurrence after 5 years, while ER+ patients had disease recurrence even after 15 years. Long term therapy should have further evaluation in premenopausal patients with ER+ tumors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-06.

Accurate Staging with Internal Mammary Chain Sentinel Node Biopsy for Breast Cancer

Although internal mammary chain (IMC) metastases are an independent predictor of prognosis, collecting IMC sentinel nodes (SN) remains controversial. We sought to determine predictors for IMC nodal positivity and the role positive IMC-SNs have on changing staging and management. We reviewed a prospectively collected database (1997-2012) to identify patients who had IMC drainage detected on lymphoscintigraphy and underwent biopsy. Chi square tests and logistic regression models were used to determine trends and factors associated with IMC node positivity. A total of 122 patients with cTis-T2cN0M0 breast cancer underwent IMC-SN biopsy. Mean age of the cohort was 53 years, and mean tumor size was 2.0 cm. Identification of IMC nodes was successful in 100% of the cases. There were no complications. Sentinel nodes mapped to the IMC alone in 14 of 122 (11%) patients. Overall, 26% of patients were node positive, with 12 of 122 (10%) patients having a positive IMC-SN. In patients with a positive axilla, IMC-SN was positive in 33% of patients, whereas in patients with a negative axilla, IMC-SN was positive in 3% of cases (P < 0.001). The number of positive axillary nodes was the only independent predictor of IMC positivity (1-3 positive axillary nodes odds ratio 16.9, 95% CI 3.1-91.1; ≥4 positive axillary nodes odds ratio 45.0, 95% CI 4.0-500.7). IMC-SN positivity led to a more advanced nodal category in all patients and more accurate staging in 4 of 12 (33%) patients. IMC-SN biopsy is predictable and safe. Identification of IMC metastases though IMC-SN biopsy has the potential to alter the stage and adjuvant therapy of breast cancer patients.

The effects of ECE on the benefits of PMRT for breast cancer patients with positive axillary nodes

BackgroundThe purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1–3, 4–9 and ≥10 positive axillary nodes). Methods: A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as ‘Radio + /ECE + ’, ‘Radio–/ECE + ’, ‘Radio + /ECE–’ or ‘Radio–/ECE–’ according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. Results: ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1–3 (P = 0.5720), ≥10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4–9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). Conclusion: In our study, regardless of the ECE status, PMRT didn't significantly improve the LRFFS for patients with 1–3 or ≥10 positive axillary nodes. However, for patients with 4–9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.