Axillary pCR Research Articles

Abstract PS6-54: Prognostic significance of residual micrometastatic axillary involvement with complete pathologic breast response after neoadjuvant chemotherapy for early breast cancer

Abstract Introduction and objectives Pathologic complete response (pCR, ypT0/Tis ypN0) after neoadjuvant chemotherapy (nCT) in early breast cancer (BC) is associated with higher survival rate. Controversy about the prognostic significance of low-volume or micrometastatic axillary residual disease (ypN1mi-RD) exists. Essentially, it is considered equivalent to high-volume nodal disease (ypN1/ypN2-RD) for the indication of lymphadenectomy after nCT. Clarifying ypN1mi-RD prognostic value would be useful for planning adjuvant therapy. Thus, our objective was to assess the prognostic significance of ypN1mi-RD in the context of primary breast tumor pCR. Material and methodsRetrospective, single-center analysis of a cohort of early BC patients treated with nCT between 2010 and 2018 who achieved breast pCR (ypT0/Tis) combined with axillary pCR (ypN0) or ypN1mi-RD or ypN1/ypN2-RD. Cases with pre-nCT sentinel lymph node biopsy were excluded. 5-year disease-free survival (DFS) and overall survival (OS) were analyzed using Cox regression models.ResultsAmong 470 early BC patients treated with nCT, 134 (28.5%) had in-breast pCR, of whom: 97 (20.6%) were ypN0; 7 (1.5%) were ypN1mic; 10 (2.1%) were ypN1 and 5 (1.1%) were ypN2. Clinicopathological characteristics of the groups are shown in the Table. Median follow-up: 33 months. Eight patients relapsed, 4 of 97 with nodal pCR and 4 of 22 with axillary residual disease: 2/7 ypN1mic; 1/10 ypN1 and 1/5 ypN2. Patients who relapsed predominantly presented pre-nCT clinical lymph node involvement, hormone receptor negativity, ki67<20% and absence of complete clinical response (100%). Globally, patients with axillary residual disease had lower DFS rates (95% vs. 69%, p = 0.03), with no apparent differences between ypN1-RD vs. ypN2-RD in the subgroup analysis (75% vs. 80%, respectively). ypN1mic-RD patients showed the poorest DFS (33%, p <0.01). In the multivariable analysis, ypN1mic-RD had worse DFS than nodal pCR (HR 13.98, 95%CI 1.95-100.24, p = 0.01), but no differences were observed between the low and high-volume residual axillary disease categories (HR 0.24, 95%CI 0.03-1.74, p = 0.16). Due to the low rate of events, no differences in terms of OS were observed (p = 0.77).Conclusion In the context of in-breast pCR after nCT for early BC, ypN1mic-RD not only presented a higher risk of relapse than nodal pCR, but also was not associated with a better prognosis than that observed for ypN1/ypN2-RD. Micrometastatic axillary residual disease behaves as an independent adverse prognostic factor, comparable to high-volume axillary residual disease, and might be considered as a factor for the indication of post-nCT adjuvant treatment. Table. Clinicopathologic characteristics of the cohort of early BC patients treated with nCT betweenypT0/TisypT0/TisypN1mic-RDypN1/N2-RDpCR(N=7)(N=15)(N=97)Age (median, range)49 (25-83)47 (40-77)47 (25-80)Menstrual statusPostmenopausal3 (42,8%)4 (26,7%)42 (43,3%)Premenopausal4 (57,1%)11 (73,3%)55 (56,7%)ECOGECOG 05 (71,4%)13 (86,7%)78 (80,4%)ECOG 12 (28,5%)2 (13,3%)19 (19,6%)Histologic subtypeInvasive ductal carcinoma7(100,0%)14 (93,3%)95 (97,9%)Other subtypes0 (0,0%)1 (6,7%)2 (2,0%)Histologic gradeGrade 10 (0,0%)0 (0,0%)1 (1,0%)Grade 23 (42,9%)5 (33,3%)17 (17,5%)Grade 34 (57,1%)8 (53,3%)67 (69,1%)Unknown0 (0,0%)2 (13,3%)0 (0,0%)cTcT11 (14,2%)4 (26,7%)8 (8,2%)cT24 (57,1%)5 (33,3%)63 (64,9%)cT32 (28,6%)6 (40,0%)24 (24,7%)cT4a-d0 (0,0%)0 (0,0%)2 (2,1%)cNcN01 (14,3%)0 (0,0%)27 (27,8%)cN13 (42,9%)5 (33,3%)34 (35,1%)cN21 (14,3%)6 (40,0%)24 (24,7%)cN32 (28,6%)4 (26,7%)11 (11,3%)Molecular subtypeHR+ HER2-1 (14,3%)8 (53,3%)11 (11,3%)HR+ HER2+3 (42,9%)1 (6,7%)30 (30,9%)HR- HER2+2 (28,6%)3 (20,0%)21 (21,6%)TNBC1 (14,3%)3 (20,0%)35 (36,1%)Breast surgeryConservative7 (100%)10 (66,7%)67 (69,1%)Mastectomy0 (0,0%)5 (33,3%)30 (30,9%)Nodal surgerySLN biopsy0 (0,0%)0 (0,0%)22 (22,7%)ALND7 (100,0%)15 (100,0%)75 (77,3%)ypTypT05 (71,4%)7 (46,7%)80 (82,5%)ypTis2 (28,6%)8 (53,3%)17 (17,5%)Relapse typeMetastatic2 (28,6%)2 (28,6%)2 (2,1%)Local/contralateral0 (0,0%)0 (0,0%)2 (2,1%)Deaths0 (0,0%)1 (6,7%)1 (1,0%)BC: breast cancer. HR: hormone receptor. nCT: neoadjuvant chemotherapy. pCR: pathologic complete response. SLN: sentinel lymph node. TN: triple negative. ypN1mic-RD: micrometastatic axillary residual disease. ypN1/N2-RD: high-volume axillary residual disease. Citation Format: Esmeralda García-Torralba, Maria Esperanza Guirao Garcia, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elena Garcia Martinez, Elisa Garcia Garre, Gema Marin Zafra, Beatriz Alvarez Abril, Esther Navarro Manzano, Francisco Ayala de la Peña. Prognostic significance of residual micrometastatic axillary involvement with complete pathologic breast response after neoadjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-54.

Abstract PS13-19: Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype

Abstract Introduction: Axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) confers higher overall and recurrence-free survival, compared to residual axillary disease. Recent findings suggest that pCR in the breast (ypT0) post-NAC is associated with a pathologically negative axilla (ypN0) in patients (pts) presenting with lower stage HER2+ and triple negative breast cancer (TNBC). Additional studies are needed to understand how clinical T (cT) and N (cN) staging are associated with ypN0 in other tumor subtypes, including hormone-receptor (HR) positive tumors. The ability to reliably predict axillary pathologic response post-NAC may allow identification of a subset of pts for whom axillary staging may be safely omitted. We hypothesize that tumor subtype and lower clinical stage at presentation are associated with ypN0. Methods: A single institution cancer registry was retrospectively reviewed for pts receiving NAC followed by surgery from January 2010-June 2018. Fisher’s exact tests were used to compared proportion of breast and axillary pCR by tumor subtype (TNBC, HR+/HER2-, HR+/HER2+ and HR-/HER2+). Univariable logistic regression determined factors associated with ypN0. Multivariable logistic regression determined the association between ypN0 and tumor subtype adjusting for factors that retained significance on univariable analysis. Sensitivity analyses determined how cN status affected ypN status by tumor subtype. Results: Of the 1348 pts who received NAC followed by surgery, median age was 54 (IQR 44-63); 59% (n=738) were postmenopausal. Proportion of tumor subtypes were: 15% (n=197) TNBC, 12% (n=155) HR+/HER2-, 48% (n=653) HR+/HER2+, and 25% (n=343) HR-/HER2+. Tumor size at diagnosis was: 1% (n=18) T0, 20% (n=272) T1, 53% (n=713) T2, 17% (n=230) T3 and 9% (n=111) T4. Clinical nodal staging at diagnosis was: 52% cN0 (n=695), 41% cN1 (n=550), 5% cN2 (n=61), and 3% cN3 (n=43). TNBC and HER2+ subtypes were associated with the highest rate of breast pCR and ypN0. On univariable analyses of the cN positive pts, younger age at diagnosis, non-postmenopausal status, oral contraceptive use, alcohol consumption, cT stage, cN stage and tumor subtype were significantly associated with ypN0 (Table1A). In the adjusted model, postmenopausal status, cT, and tumor subtype were associated with ypN0. Lower cT and HR- subtypes had significantly higher odds of ypN0 (Table 1B). In sensitivity analyses, cN2/cN3 was associated with lower odds of ypN0 compared to cN0/cN1 disease in TNBC (OR0.11 95%CI 0.03,0.40, p=0.001), HR-/HER2+ disease (OR0.42, 95%CI 0.22,0.77, p=0.005), and HR+/HER2+ (OR0.26 95%CI 0.11,0.61 p=0.002), but not in HR+/HER2- disease (OR1.17, 95%CI 0.25,5.57, p=0.838). Conclusion: HR- and low cT stage at diagnosis are associated with ypN0 in this large cohort. Younger age, pre-menopausal status and cN stage may be important considerations in future investigations aimed at defining the subset of patients most likely to achieve ypN0 and ultimately to be considered for de-escalation of axillary staging post NAC. A.Univariable logistic regression analysisVariableOdds Ratio95% Confidence Intervalp valueAge at diagnosis0.990.98, 0.99<0.001RaceWhite1.060.70, 1.600.777Black0.600.17, 2.080.421Asian1.200.36, 4.000.768Postmenopausal0.760.60, 0.960.023BMI1.000.99. 1.000.424Oral contraceptive use1.250.95, 1.630.114Alcohol consumption1.601.05, 2.440.027 Tobacco use1.130.99, 1.290.064Family history of cancer1.250.92, 1.680.148Grade12.170.75, 6.250.15320.950.45, 2.010.89131.700.81, 3.590.163HistologyIDC1.451.10, 1.890.007ILC0.370.23, 0.60<0.001Mixed0.950.68, 1.320.764Other0.440.18, 1.080.073Clinical T stage11.370.47, 3.980.56920.760.27, 2.160.60530.350.12, 1.020.05540.150.05, 0.450.001Clinical N stage10.140.11, 0.18<0.00120.130.07, 0.23<0.00130.110.06, 0.21<0.001Tumor subtypeTNBC1.591.00, 2.530.049HR+/ HER2 -0.550.35, 0.870.010HR+/ HER2+0.690.47, 1.000.049HR-/ HER2 +1.641.09, 2.460.019B.Multivariable logistic regression analysisAge at diagnosis0.980.97, 0.99<0.001Alcohol use1.190.74, 1.930.476HistologyIDC1.150.82, 1.610.414ILC0.570.32, 1.010.053Mixed1.080.71, 1.630.721Other0.790.28, 2.220.660Clinical T stage11.190.39, 3.580.76120.740.25, 2.160.58530.510.17, 1.540.23540.290.09, 0.910.034Clinical N stage10.130.10, 0.18<0.00120.140.08, 0.26<0.00130.100.05, 0.20<0.001Tumor subtypeTNBC1.440.84, 2.470.181HR+/ HER2 -0.540.31, 0.940.028HR+/ HER2+0.600.39, 0.930.024HR-/ HER2 +1.701.05, 2.730.030 Citation Format: Sara P Myers, Gillian M Ahrendt, Joanna S Lee, Jennifer G Steiman, Atilla Soran, Ronald R Johnson, Priscilla F McAuliffe, Emilia J Diego. Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-19.

Abstract PS3-09: The use of magnetic resonance imaging (MRI) in predicting pathological complete response(pCR) in the breast and axilla after the addition of immunotherapy to neoadjuvant systemic therapy (NST)

Abstract Introduction: Immunotherapy use is increasing as an adjunct to current NST for breast cancer treatment with the goals of increasing pCR and down staging tumors. In this study, we assessed the effectiveness of MRI in the evaluation of tumor response after neoadjuvant immunotherapy in combination with NST. Methods: We retrospectively reviewed the clinicopathological data of 105 women undergoing Immunotherapy in conjunction with NST at a single institution. All patients had been enrolled in IRB approved protocols and had undergone definitive surgery. Patients were excluded for: failure to complete at least two thirds of treatment, no pre or post treatment MRI, or surgery in an outside institution. We analyzed 73 patients from 5 distinct treatment protocols including: (1) 24 Triple negative breast cancer (TNBC) patients (pts) treated with Intratumoral Talimogene laherparepvec (TVEC) in combination with weekly paclitaxel followed by dose dense Adriamycin and Cytoxan (ddAC); (2) 19 HER2/Neu positive (HER2+) pts treated with subcutaneous interferon gamma (IFN-γ) in combination with weekly paclitaxel with trastuzumab and pertuzumab (HP); (3), 7 HER2+ pts treated with 3 weeks of HER2 pulsed dendritic cell vaccines (DC1) followed by Taxotere, Carboplatin, and HP; (4), 14 pts on the ISPY2 trial: 8 TNBC and 4 Hormone receptor positive, HER2/Neu negative (HR+) pts randomized to treatment with pembrolizumab with weekly paclitaxel followed by ddAC (2 also received additional SD101), and 2 TNBC pts treated with Durvalumab, Olaparib and Paclitaxel, followed by ddAC and (5) 9 HR+ pts on neoadjuvant Durvalumab and an Aromatase Inhibitor for 6 cycles. Results: A total of 73 patients were included in the study. Median age was 51 years (range 27-76); 46.6% of patients had TNBC, 35.6% had HER2+ and the remaining 17.8% were HR+ HER2-. The median clinical tumor size was 3.4cm (range 1.3-10.6) pre therapy and 1cm (range 0-10.1) post therapy. The pCR was 38.2%, 57.7%, and 0% respectively for TNBC, HER2+, HR+ tumors. Complete radiological response (rCR) of both the axilla and breast was 41.2%, 61.5% and 7.7%, for TNBC, HER2+ and HR+ tumors. The sensitivity of MRI to detect in breast pCR was 65.6% with a specificity of 81%, NPV and PPV of 75% and 73.3% respectively. MRI identified 37 pts with suspicious axillary nodes on pretreatment MRI; of these 30 had fine needle aspiration (FNA) confirmed metastatic disease. Post treatment, 70.3% (26/37) had normalized axillary nodes. Of those with normalized nodes, 26.9% (7/26) had residual cancer on final pathology. Of the patients with confirmed FNA lymph node metastasis, axillary pCR of 63.3% was achieved. The sensitivity and specificity of MRI to detect pCR within the axilla was 87% and 50% and NPV and PPV 70% and 74.1%, respectively. 3 patients had axillary disease on final pathology but no suspicious imaging and a benign FNA. Conclusion: The addition of immunotherapy to current NST strategies can improve pCR and decrease residual cancer burden. The PPV and NPV of MRI to predict pCR in patients undergoing immunotherapy in combination with NST remains within the ranges described in patients undergoing NST alone. MRI remains a useful tool to guide surgical management but is not accurate enough to replace pathological evaluation. Citation Format: Noeline Rajarajan, Daniel Segarra, Robert J Weinfurtner, Adrian A Lopez, M Catherine Lee, John Kiluk, Hatem Soliman, Hung Khong, Han S Hyo, Marilin Rosa, Brian J Czerniecki, Nazanin Khakpour. The use of magnetic resonance imaging (MRI) in predicting pathological complete response(pCR) in the breast and axilla after the addition of immunotherapy to neoadjuvant systemic therapy (NST) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-09.

Abstract PS14-21: Refining loco-regional therapy for inflammatory breast cancer protocol in progress

Abstract Background: Inflammatory breast cancer (IBC) is the most aggressive locally advanced breast cancer subtype. It is associated with loco-regional recurrence rates of 12-25%, and neoadjuvant chemotherapy (NAC) followed by modified radical mastectomy and comprehensive chest wall and regional nodal radiotherapy remain the standard of care. As has been demonstrated in non-IBC, achievement of pathologic complete response (pCR) has been shown to be associated with improved loco-regional control, recurrence-free and overall survival. Advances in NAC for IBC have resulted in improved pCR rates in both the breast and the axilla, with overall axillary pCR rates of approximately 30%, reaching as high as 67% in patients with HER2-positive disease receiving HER2-directed therapy. Hypothesis: Sentinel lymph node biopsy (SLNB) may be feasible in IBC patients who experience a good clinical and pathologic response in the axilla to NAC. Primary Objective: To evaluate the sentinel lymph node (SLN) identification rate in stage III IBC patients who experience cN0 status at completion of NAC. Secondary Objective: To assess the incidence of lymphedema following standard local-regional therapy for IBC. Methods and Study procedures: In this feasibility study, 50 patients with cT4dN0-2M0 IBC will be enrolled in order to evaluate 40 patients whose axillary nodal status becomes cN0 upon completion of NAC. All patients will undergo a research breast biopsy and lymphoscintigram pre and post NAC to evaluate lymphatic drainage patterns and patency of breast and axillary lymphatics. Post NAC lymphoscintigraphy will be appropriately timed for pre-operative SLN mapping and all patients will undergo SLNB using dual tracers (Tc99 Sulfur colloid and blue dye) with immediate axillary lymph node dissection (ALND), at the time of mastectomy. The patient-reported Lymphedema Symptom Intensity and Distress Survey (LSIDS-A) will be collected at 6 timepoints. Patients will be followed for 2 years post-surgery for oncologic outcomes. Correlatives: We plan to evaluate genetic and phenotypic heterogeneity in IBC and to assess markers of angiogenesis and lymph-angiogenesis associated with IBC, as well as to explore immunologic aspects of the tumor microenvironment and their association with pCR. Statistics: The identification rate will be calculated as number of patients in whom SLNs were successfully identified over the number of patients with cN0 disease after NAC in whom SLN mapping was attempted. Using a Simon two-stage design (α=.10, β=.10), a SLN identification rate of ≥90% would result in considering this procedure feasible whereas an identification rate of ≤75% (null hypothesis) would lead to the conclusion that it is not feasible. In the first stage, if greater than 18 of 25 patients have SLNs identified, then a total of 40 patients will be enrolled. If fewer than 33 of 40 patients have SLN identified, then the null hypothesis is rejected. Citation Format: Faina Nakhlis, Meredith Regan, Heather Jacene, Beth Harrison, Jennifer Bellon, Jean Landry, Eren Yeh, Elizabeth Mittendorf, Beth Overmoyer, Tari King. Refining loco-regional therapy for inflammatory breast cancer protocol in progress [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-21.

Diagnostic Accuracy of Axillary Ultrasound for Prediction of Axillary Pathologic Response after Neoadjuvant Treatment in Breast Cancer.

Background: In the era of NAT, to accurately predict pathologic response is a great challenge, which might influence surgical approach for breast and axilla. Axillary staging via imaging methods as an adjunct have long been used with various reported accuracy rates. However, the role of preoperative axillary ultrasonography (AUS) in clinical N0 patients after NAT is still controversial. The primary goal of the present study was to evaluate the precision of preoperative AUS for identifying pathologic complete response (ypCR = ypT0, ypN0) after NAT. Methods: A single-institution, retrospective review of a prospectively maintained database was analyzed to identify breast cancer patients treated with NAT. Only those patients who underwent AUS and 18F-FDG-PET/CT before and after NAT with documentation of clinical and radiological response were incorporated for outcome analysis. Results: In 253 consecutive invasive breast cancer patients axillary ypN0 disease was achieved in 67.19%. In 11.23% ynon-pCR patients AUS failed to detect residual disease presence 80% of which were ITCs and micrometastases. Macrometastasis was present in 21.73% (55/253) of the cases 98.18% (54/55) of which was determined by AUS. Overall accuracy for axillary pCR was found to be 89.32% for AUS and 76.28 % for 18-FDG-PET/CT. The false negative rate (FNR) of AUS and 18-FDG-PET/CT was 12.04% and 15.59%, respectively. The PPV of AUS was higher in Luminal-like tumors (%87.69), whereas HER-2 positive (%100) and triple-negative (93.47%) subtypes had higher NPV. Conclusions: AUS is a beneficial tool with the potential of accurate prediction of pCR in more than 80% of patients following NAT. Nevertheless, in cases of residual ITCs and micrometastasis the accuracy of US should be interrogated cautiously.

The Role of Oncotype DX® Recurrence Score in Predicting Axillary Response After Neoadjuvant Chemotherapy in Breast Cancer.

Oncotype DX® recurrence score (RS) is well-recognized for guiding decision making in adjuvant chemotherapy; however, the predictive capability of this genomic assay in determining axillary response to neoadjuvant chemotherapy (NCT) has not been established. Using the National Cancer Data Base (NCDB), we identified patients diagnosed with T1-T2, clinically N1/N2, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER +/HER2 -) invasive ductal carcinoma of the breast between 2010 and 2015. Patients with an Oncotype DX® RS who received NCT were included. RS was defined as low (< 18), intermediate (18-30), or high (> 30). Unadjusted and adjusted analyses were performed to determine the association between axillary pathologic complete response (pCR) and RS. This study included a total of 158 women. RS was low in 56 (35.4%) patients, intermediate in 62 (39.2%) patients, and high in 40 (25.3%) patients. The majority of patients presented with clinical N1 disease (89.2%). Axillary pCR was achieved in 23 (14.6%) patients. When stratifying patients with axillary pCR by RS, 11 (47.8%) patients had a high RS, 6 (26.1%) patients had an intermediate RS, and 6 (26.1%) patients had a low RS. Comparing cohorts by RS, 27.5% of patients with high RS tumors had an axillary pCR, compared with only 9.7% in the intermediate RS group, and 10.7% in the low RS group (p = 0.0268). Our findings demonstrate that Oncotype DX® RS is an independent predictor of axillary pCR in patients with ER +/HER2 - breast cancers receiving NCT. A greater proportion of patients with a high RS achieved axillary pCR. These results support Oncotype DX® as a tool to improve clinical decision making in axillary management.

Discrepancy of Breast and Axillary Pathologic Complete Response and Outcomes in Different Subtypes of Node-positive Breast Cancer after Neoadjuvant Chemotherapy.

Few studies have analyzed the discrepancy between breast pathologic complete response (B-pCR) and axillary node pCR (N-pCR) rates and their impact on survival outcomes in different intrinsic subtypes of early breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively reviewed B-pCR, N-pCR, and total (breast and axillary node) pCR (T-pCR) after NAC to assess the discrepancy and outcomes between 2005 and 2017. A total of 968 patients diagnosed with cT1-4c, N1-2, and M0 breast cancer were enrolled in the study. The median age was 49 years and the median follow-up time was 45 months. Of these patients, 213 achieved T-pCR, 31 achieved B-pCR with axillary node pathologic non-complete response (N-non pCR), 245 achieved N-pCR with breast pathologic non-complete response (B-non pCR), and 479 achieved total (breast and axillary node) pathologic non-complete response (T-non pCR) after NAC. The highest B-pCR and N-pCR rates were found in the hormone receptor-negative, human epidermal growth factor receptor 2-positive HR(-)HER2(+) subtype, while the lowest B-pCR rate was found in the HR(+)HER2(-) subtype. The N-pCR rate was correlated to the B-pCR rate (P<0.001), but was higher than the B-pCR rate in all subtypes. The 5-year overall survival (OS) rates for patients with T-pCR, B-pCR, and N-pCR were 91.2%, 91.7%, and 91.9%, respectively. For non-pCR, non-pCR, and non-pCR, the 5-year OS rates were 73.6%, 78.9%, and 74.7%, respectively (P<0.0001). B-non pCR patients had a lower risk of recurrence than T-non pCR or N-non-pCR patients, although there were no differences in OS among them. In conclusion, the N-pCR rate was higher than the B-pCR rate after NAC in all intrinsic subtypes, and N-non pCR or T-non pCR patients had the worst outcomes.

Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy. A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present. Clinical and radiological responses after NACT were also evaluated. Univariate and multivariate analyses by logistic regression were performed. Distant disease-free survival (DDFS) was calculated in relation to the status of the axillary lymph nodes after NACT. After NACT, 89 patients (40.3%) had axillary pathologic complete response (pCR) (ypN0) and 132 (59.7%) had residual axillary disease (ypN+). Molecular surrogate subtype, Ki-67 expression, and the clinical and radiological responses to NACT were the only independent factors associated with ypN0. Axillary pCR was observed more often in HER2-positive and triple-negative tumours than in luminal ones (OR 7.5 and 3.6, respectively). DDFS was 88.7% (95% CI 80.7-96.7%) for ypN0 and 56.2% (95% CI 32.1-80.3%) for ypN+ (p = 0.09). In HER2-positive and triple-negative breast cancer patients staged as cN2 or with high axillary burden before NACT, a sentinel lymph node biopsy after NACT could be recommended if there is a clinical and radiological response.

Leveraging the increased rates of pathologic complete response after neoadjuvant treatment in breast cancer to de-escalate surgical treatments.

Breast conservative surgery (BCS) and sentinel lymph node biopsy (SLNB) after neoadjuvant treatment (NAT) is safe and effective for selected patients. This aim of this study is to evaluate the impact of anatomic site of response on outcomes and to assess the real population who may benefit from nonsurgical approaches after NAT. From a prospectively maintained database, patients with T1-4 N0-2 breast cancer undergoing NAT were identified. Clinicopathological and survival rates were compared in relation to response and anatomic site of response. Six hundred and forty-six patients were included in the study. Pathologic complete response (pCR) was an independent factor for BCS and SLN. HER2 positive and TN tumors with cN0 achieving a breast pCR remain ypN0 (p = .002). Residual axillary disease was associated with breast residual tumor (p = .05) and subtype (p = .001). With a median follow up of 35.25 months, patients with any pCR had improved survival when compared with partial response, but not significant differences between pCR, axillary pCR, or breast pCR. Achieving a pCR increases BCS and SLN. In selected subgroups, sparing any axillary surgery after NAT maybe feasible. In cN+ patients, any pCR was associated with survival, but not the anatomic site of response.

Pathological Complete Response with Neoadjuvant Trastuzumab Combined with Chemotherapy in HER2 Positive Breast Cancer: A Single Institution Retrospective Analysis from Vietnam.

PurposeNeoadjuvant regimens containing trastuzumab and chemotherapy were widely used in human epidermal growth factor 2 (HER2) positive breast cancer patients. In this article, we report complete pathological response (pCR) rates from a single institution in Vietnam.Patients and MethodsMedical records of HER2 positive breast cancer patients who received neoadjuvant treatment with trastuzumab combined with chemotherapy were reviewed. Information on patient demographics, breast cancer stage, pathology reports, surgical data, and treatment regimens were collected. Pathological response was evaluated using Chevallier’s criteria, in which complete pathological response was defined as yT0yN0 or yTisN0.ResultsThirty-nine eligible breast cancer patients treated with chemo-trastuzumab combined regimens in a neoadjuvant setting at Vietnam National Cancer Hospital were included in the analysis. Median age was 47 (range 32–72 years). Of these 39 patients, 5 (12.8%) were at stage II and 34 (87.2%) were at stage III. Median tumor size was 5.8 cm. There were 22 (56.4%) and 17 (43.6%) patients who had hormone receptor (HR) negative and positive diseases, respectively. Pathological complete response in the breast was demonstrated in 30 out of 39 (76.9%) patients. Of 35 patients with lymph nodal involvement, axillary pCR occurred in 25 (71.4%) patients. Total pathological complete response (tpCR) was achieved in 25 (64.1%) of the evaluated patients. There was no significant association between pathological response rates and age, tumor grade, hormone receptor status, and Ki-67 expression.ConclusionNeoadjuvant treatment with trastuzumab and chemotherapy combined in patients with HER2 positive breast cancer yielded a pathological complete response rate of 64.1%.

Survival in Cytologically Proven Node-Positive Breast Cancer Patients with Nodal Pathological Complete Response after Neoadjuvant Chemotherapy.

Simple SummaryIt is unknown whether patients with cytologically proven axillary node-positive breast cancer, who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC. The aim of this retrospective study was to clarify the clinical impact of axillary pCR after NAC on survival and to compare survival outcomes between breast cancer patients with axillary pCR, and those with axillary pN- without NAC, using propensity score matching to adjust for baseline characteristics other than nodal status. Axillary pCR after NAC was associated with improved prognosis in patients with axillary node-positive disease, and patients with axillary pCR and matched pairs with axillary pN- without NAC had comparable outcomes.Background: It is unknown whether patients with cytologically proven axillary node-positive breast cancer who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC. Methods: We retrospectively reviewed the data of patients with cytologically proven axillary node-positive disease who received NAC and those with axillary pN- without NAC for control between January 2007 and December 2012. We compared outcomes according to response in the axilla to NAC and between patients with axillary pCR and matched pairs with axillary pN- without NAC using propensity scores. Results: We included 596 patients with node-positive breast cancer who received NAC. The median follow-up period was 64 months. Patients with axillary pCR showed significantly better distant disease-free survival (DDFS) and overall survival (OS) than patients with residual axillary disease (both p < 0.01). There was no significant difference in DDFS and OS between patients with axillary pCR and matched pairs with axillary pN- without NAC. Conclusion: Axillary pCR was associated with improved prognosis. Patients with axillary pCR and matched pairs with axillary pN- without NAC had comparable outcomes. This information will be useful when considering the intensity of follow-up and adjuvant therapy.

Breast radiologic complete response is associated with favorable survival outcomes after neoadjuvant chemotherapy in breast cancer

BackgroundThe aim of this study was to examine the accuracy of radiologic complete response (rCR) in predicting pathologic complete response (pCR), and determine whether rCR is a predictor of favorable survival outcomes. Materials and methodsWe retrospectively reviewed breast cancer patients treated with neoadjuvant chemotherapy (NAC) followed by surgery from September 2007 to June 2016. Breast lesions and axillary nodes were measured by MRI and categorized into either disappeared (breast rCR) or residual disease (breast non-rCR) and either normalized (axillary rCR) or abnormal findings (axillary non-rCR) in the axillary nodes. Correlation between rCR and pCR were compared using Cohen’s Kappa statistics, and the recurrence-free survival (RFS) and overall survival (OS) rates were calculated by the Kaplan-Meier method. ResultsOut of the 1017 eligible patients, 287 (28.2%) achieved breast pCR, 165 (16.2%) achieved breast rCR, 529 (52.0%) had axillary pCR, and 274 (26.9%) achieved axillary rCR. The correlation between a breast rCR and pCR showed a Cohen’s Kappa value of 0.459, and between axillary rCR and pCR, the value was 0.384. During a median follow-up time of 48.0 months, the 5-year RFS rates were 90.6% for breast rCR, and 69.2% for breast non-rCR. The 5-year RFS rates were 82.3% for axillary rCR, and 68.8% for axillary non-rCR. Patients without breast rCR had a 2.4-fold significant increase in the risk of recurrence (p = 0.004) compared to patients with breast rCR. ConclusionAlthough rCR correlated with pCR by only moderate to fair degrees, breast rCR was a strong predictor for a favorable RFS outcome.

Axillary Response in Patients Undergoing Neoadjuvant Endocrine Treatment for Node-Positive Breast Cancer: Systematic Literature Review and NCDB Analysis

BackgroundSeveral studies have proven that neoadjuvant endocrine therapy (NET) has a similar beneficial therapeutic effect in estrogen-positive (ER+) breast cancer (BC) with improved breast conservation rate in patients undergoing NET versus neoadjuvant chemotherapy (NAC). The impact of axillary complete pathologic response (pCR) is less clear. We evaluate the impact of NET on axillary downstaging and surgical management.MethodsUsing the National Cancer Database (NCDB), we identified all patients with node positive (N+), ER+, HER2− BC undergoing NET and performed a systemic review of literature using PRISMA guidelines.ResultsThe literature review identified 1479 clinically N+ patients in four studies, 148 of whom had axillary pCR (10.0%). In the two studies of patients with invasive lobular carcinoma (ILC), 7.8% (69/883) of clinically N+ patients had axillary pCR. The NCDB query identified 4580 female patients with clinically N+ ER+ HER2− BC who underwent NET from 2010 to 2016 with mean age of 61.4 years. Patients who achieved a pCR were more likely to have N1 disease (p 0.008), moderately differentiated tumors (p 0.003), and ductal histology (p 0.04). There was no statistically significant difference in race, comorbidity score, education, income, hospital setting, or clinical tumor stage. Of the 4580 total patients, 663 (14.48%) had an axillary pCR (pN0) after NET, and 3917 (85.52%) remained pN+.ConclusionsWe found that patients who underwent NET for N+ disease had a higher axillary pCR than previously reported (10%) in smaller studies. Although NET is not a common treatment option for women with N+ ER+ HER2− BC, it may be a suitable option for axillary downstaging, which is currently underutilized.Electronic supplementary materialThe online version of this article (10.1245/s10434-020-08905-9) contains supplementary material, which is available to authorized users.

Association of higher axillary pathologic complete response rate with breast pathologic complete response after neoadjuvant chemotherapy.

BackgroundTo investigate the association of axillary pathologic complete response (pCR) rate among breast cancer patients with pCR after neoadjuvant chemotherapy (NCT).MethodsThe retrospective clinical data of 1,903 patients who were treated with NCT between March, 2010 and December, 2018, were collected from one Chinese database and analyzed. The correlations between clinicopathological characteristics and breast pCR with axillary pCR were calculated by χ2 test. Binary logistic regression analysis was used for multivariate analysis. The relative risk of positive axillary nodes after NCT in patients with and without breast pCR was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by initial N stage and tumor subtype.ResultsThe rate of axillary pCR was increased in the cases with initial cN0, Ki67 high expression, HR+HER2+/HR-HER2+/TN subtypes, and breast pCR. After NCT, the relative risk of nodal disease burden was 4.81 in patients without breast pCR compared with patients with breast pCR. The relative risk of positive nodal status in patients with cN0, cN1, cN2, and cN3 disease without vs. with breast pCR was 6.45, 4.88, 5.69 and 6.24, respectively. The relative risk of positive nodal status in patients with HR+HER2−, HR+HER2+, HR−HER2+, and TN disease was 4.02, 4.50, 3.82 and 4.18, respectively. Of cN0 patients with breast pCR, only 4 out of 44 (9%) with HER2-positive disease had 1 or 2 axillary lymph node metastases at final surgical pathology compared to 30 out of 98 (31%) of those without breast pCR. There was no evidence of positive nodal residue among all 21 patients (100%) with TN disease compared to 65% (36 of 55) of patients without breast pCR.ConclusionsNodal status is strongly correlated with breast pCR after NCT. Patients with initial cN0/1 TN/HER2 positive disease who achieve breast pCR at surgery have a low risk of nodal metastasis. These results suggest that the failure rate of missing positive lymph nodes among those patients was very low and that it is safe for such patients to undergo sentinel lymph node biopsy (SLNB) after NCT. This study also provides a theoretical basis for clinical trials focused on the avoidance of axillary surgery in selected patients.

A nomogram for predicting axillary pathologic complete response in hormone receptor–positive breast cancer with cytologically proven axillary lymph node metastases

The objective of this study was to determine an axillary pathologic complete response (pCR) and its influencing factors in patients with hormone receptor (HR)-positive breast cancer and cytologically proven axillary lymph node metastases. A prediction nomogram was established to provide information for the de-escalation of axillary management in these patients after neoadjuvant chemotherapy. The authors retrospectively enrolled all patients with HR-positive breast cancer in the neoadjuvant chemotherapy data set of Fudan University Shanghai Cancer Center. All data were prospectively collected. From 2007 to 2016, 533 consecutive patients were included. Multivariate logistic regression analysis was performed, after which a nomogram was constructed and validated. An axillary pCR was achieved in 168 patients (31.5%), the which was much higher than the proportion of those who achieved a breast pCR (103 patients; 19.3%). Patients who had human epidermal growth factor receptor 2-positive disease (P=.004), a better primary tumor response (P=.001), earlier clinical stage (P=.045), and lower estrogen receptor expression (P<.001) were more likely to achieve a lymph node pCR. The nomogram indicated an area under the receiver operating characteristic curve (AUC) of 0.84 (95% CI, 0.78-0.89) in the training set. The validation set showed good discrimination with an AUC of 0.75 (95% CI, 0.69-0.81). The C-index was 0.834 and 0.756 in the training and validation cohort, respectively. The nomogram was well calibrated. The authors developed and validated a nomogram for predicting axillary pCR in patients with HR-positive disease accurately by using clinicopathologic factors available before surgery. The model will facilitate logical clinical decision making and clinical trial design.

Impact of progesterone receptor status on response to neoadjuvant chemotherapy in estrogen receptor-positive breast cancer patients.

Breast cancer patients respond differently to neoadjuvant chemotherapy(NAC) based on receptor subtype. The aim of this study was to assess the impact of progesterone receptor (PgR) status on response to neoadjuvant chemotherapy (NAC) in estrogen receptor (ER)+, human epidermal growth factor receptor (HER)- breast cancer patients. ER+ and HER- patients receiving NAC over a 7-year period (2011-2017) were identified. The primary outcome was breast complete pathological response (pCR) rate. Secondary outcomes included axillary pCR, axillary/breast pCR and complete radiological response (cRR). A total of 203 patients were identified (149 in the ER+, PgR+, and HER- group and 54 in the ER+, PgR-, and HER- group). Compared with the PgR+ group, PgR- patients were significantly associated with breast pCR (31.5% vs 7.4%; χ² test; P < .01). In multivariable analysis, PgR- status (odds ratio [OR], 4.58; 95% confidence interval [CI]: 1.58,13.28; P = .005), radiological size >50 mm (OR, 5.38; 95% CI: 1.07,27.04; P = .04) and grade (OR, 3.52;95% CI: 1.21,10.23;P = .02) were significant predictors of breast pCR. Only PgR- status was a significant predictor of cRR (OR, 6.234; 95% CI: 2.531, 15.355; P < .001). In node positive patients, PgR negativity was associated with a trend towards breast/axillary nodal pCR (22% vs 12.7%; χ² test; P = .055). Over 30% of ER+, PgR-, and HER- patients will have a breast pCR after NAC. PgR- is the only significant predictor of breast pCR/cRR in this tumor subtype. ER+, PgR-, and HER- patients should be considered for NAC.

Evaluation of Pathologic Complete Response (pCR) to Neoadjuvant Chemotherapy in Iranian Breast Cancer Patients with Estrogen Receptor Positive and HER2 Negative and impact of predicting variables on pCR.

The pathologic complete response (pCR) in the breast and axillary lymph node after neoadjuvant chemotherapy (NAC) would improve outcomes and it is used as a surrogate marker for survival. Our objective was to evaluate the breast and nodal pCR in breast cancer patients with estrogen receptor-positive (ER) and HER2 negative subtypes. Meanwhile, we sought to examine the impact of predicting factors on the rate of pCR. In this multicenter retrospective study, medical records data of 314 women with ER+/HER2- breast cancer subtype who received neoadjuvant chemotherapy was extracted from oncology centers' data between 2011 and 2018. Breast and axillary lymph node pCR were assessed. Meanwhile, receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value for proliferative index (Ki-67%) expression. Breast pCR was seen in 25.2% (n=79) of the 314 cancer patients and partial response was seen in 47.8% (n=150), too. Nodal pCR was reported in 30.9% (n=97) of the 249 node-positive patients. The overall pCR (both breast & node) was observed in 14.6 % (n=46) of the 272 patients in which the data of breast and nodal were available. We identified 22.5% as the best cut-off value for ki-67 expression in predicting complete response to NAC. The pCR rate after NAC in ER+/HER2- subtypes of breast cancer is low. Therefore, the optimal therapy for these patients should be further investigated.

Computed tomography reconstruction for evaluating response in axillary lymph nodes of breast cancer after neoadjuvant chemotherapy.

To assess the performance of computed tomography (CT) reconstruction in evaluating the response in metastatic lymph nodes after neoadjuvant chemotherapy (NAC) in breast cancer patients. Patients undergoing pre-NAC and post-NAC CT were identified from the Peking University Cancer Hospital database. Axillary Lymph nodes (ALNs) that shrunk to < 5mm in short-axis diameter after NAC on CT reconstruction images were classified as clinical complete response. Evaluations of CT reconstruction on ALNs were correlated with residual nodal disease in the final pathology. Overall, 53 invasive breast cancer patients between October 2016 and March 2018 were eligible for our study. The median age was 48 (range 35-70) years. Most women presented with T2 tumors (35/53, 66.0%). After NAC, 20 (37.7%) patients without residual nodal disease were defined as pCR. Of 53 patients, 18 (33.9%) showed negative conversion of ALNs on CT reconstruction evaluation; axillary pCR was present in 16/18 (88.9%) patients. Among 35 patients with abnormal nodes on post-NAC CT reconstruction, 31 (88.6%) had axillary metastasis on the final pathology. The sensitivity and specificity of CT reconstruction in predicting node-negative status were 80.0% and 93.9%, respectively. The positive predictive value was 84.9% for lymph node pCR. The area under the receiver operating characteristic curve of each imaging modality was 0.870 (95% confidence interval 0.755-0.984). CT reconstruction was useful for evaluating ALNs response following NAC and may be used to predict axillary nodes' pCR with adequate accuracy.

Gauging the efficacy of neoadjuvant endocrine therapy in breast cancer patients with known axillary disease.

Neoadjuvant endocrine therapy (NET) for ER+ breast cancer can downstage primary tumors. We evaluated NET efficacy in node-positive patients. Node-positive patients undergoing NET for ER+ breast cancer from 2012 to 2019 were reviewed. Primary endpoints included rates of axillary lymphadenectomy (ALND), pathologic complete response (pCR), and final nodal staging. Thirty-nine patients were included. Before NET, all were clinically node-positive (cN1 = 36, 94%; cN2 = 2, 5%; cN3 = 1, 3%; Stage II = 23, 59%, Stage III = 16, 41%). After NET, nine (23%) had clinically persistent axillary disease necessitating ALND. The remaining 30 (77%) underwent sentinel lymph node biopsy (SLNB). Of these, 25 (83%) were SLNB+ on frozen section, undergoing immediate ALND. Five patients were negative on frozen section: one had a confirmed axillary pCR, and four had residual nodal disease on permanent pathology. One underwent delayed ALND, and for the remaining three patients, decision was made to forgo ALND. Final overall axillary staging was: N0 (pCR) = 1, 3%, pN1mic = 1, 3%, pN1 = 20, 51%, pN2 = 12, 30%, pN3 = 5, 13%; Stage II = 16, 41%, Stage III = 23, 59%. While NET is reported to downstage primary tumors, downstaging of the axilla was unsuccessful in the majority of patients.

Characterization of weakly hormone receptor (HR)-positive, HER- negative breast cancer (BC) and current treatment strategies.

e12621 Background: HR and HER2 status is critical for determining initial management of BC. Current guidelines define estrogen receptor (ER) and progesterone receptor (PR)+ as ≥1%. Previous reports of small cohorts with low HR+/HER2- disease showed similar rates of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) as triple negative BC (TNBC). This study aims to further characterize this group of patients (pts), focusing on modern management and breast/axillary pCR rates following NAC. Methods: Pts with newly diagnosed stage I-III, HR+/HER2- BC from 1/1/2009–4/1/2019 were found using the University of Wisconsin Hospital and Clinics Cancer Registry. Medical records were reviewed for demographics, tumor characteristics with quantification level of ER and PR ( &lt; 33%), treatments including NAC and adjuvant chemotherapy (chemo), endocrine therapy, surgery and radiation, and follow-up clinical data. Results: Data reviewed from 2,905 pts: 2,604 (89.6%) were HR+/HER2-, 282 (9.7%) were ER+/PR-, and 19 (0.7%) were ER-/ PR+. A total of 64 pts [median age 54 (22-87), 100% female] met inclusion criteria. At diagnosis, 23 (36%) were anatomic stage 1, 30 (47%) stage II, and 11 (17%) stage III; 18 (28%) had biopsy (bx) proven nodal disease. 57 (89%) had invasive ductal carcinoma; 9 (14%) were ER+/PR+, 43 (67%) ER+/PR-, and 12 (19%) ER-/ PR+. The majority [51 (80%)] received chemo, ~ half with NAC 30 (48%), 1 pt chemo plan was unknown. NAC regimens included an anthracycline (A) and taxane (T) [26 (41%)], a sole A regimen [1 (1%)], and an A+T and platinum regimen [3 (5%)]. 4 pts received capecitabine after NAC. 50 (78%) pts had a sentinel lymph node bx, but 13 (20%) had an axillary node dissection (ALND). 10 (16%) pts did not receive any endocrine therapy, 28 (44%) got tamoxifen, 22 (34%) an aromatase inhibitor, and 4 (6%) unknown. Of 28 pts who had NAC followed by breast and axillary surgery, 12 (43%) had pCR (ypT0/Tis/ypN0). Of the 12 pts who had bx proven nodal disease at diagnosis and NAC, 7 (64%) pts had pCR at the axilla. One pt had progressive disease on NAC, 1 had local recurrence and 8 (13%) pts had distant recurrence. Median time to recurrence was 13.6 (5.6 – 48.7) months. Only 2 pts with pCR had distant recurrence. Conclusions: BC that are HER2- and weakly HR+ treated with NAC demonstrated an axillary and overall pCR rate more similar to TNBC than breast cancers with strong HR+. Neoadjuvant approaches may reduce need for ALND and pCR may provide important prognostic information. Clinical trials should be developed to focus on this unique patient cohort.