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Oncologic necessity for the complete removal of residual microcalcifications after neoadjuvant chemotherapy for breast cancer.

ABSTRACT: The surgical range of breast cancer that shows pathologic complete response (pCR) without change in microcalcifications after neoadjuvant chemotherapy (NAC) is controversial. This study examined whole breast specimens to evaluate the necessity of mastectomy in those cases. The viability of cancer cells around the residual microcalcification was assessed using prospectively collected breast samples to confirm the presence or absence of cancer cells. A total of 144 patients with breast cancer and diffuse microcalcifications were classified into the reduced mass with no change in residual microcalcification (RESMIN, n = 49) and non-RESMIN (n = 95) groups. Five specimens were prospectively evaluated to assess the presence of viable cancer cells around the microcalcification. Tumor responses to NAC were significantly better with high pCR rates in the RESMIN group (p = 0.005 and p = 0.002). The incidence of human epidermal growth factor receptor 2-positive and triple-negative breast cancers was significantly high in the RESMIN group (p = 0.007). Although five (10.2%) patients had locoregional recurrence in the RESMIN group, no local recurrence in the breast was reported. Although pCR was highly estimated, residual cancers, including ductal carcinoma in situ, remained in 80% cases. Therefore, given the weak scientific evidence available currently, complete removal of residual microcalcifications should be considered for oncologic safety.

SUBMITTER: Lee J

PROVIDER: S-EPMC9748126 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Oncologic necessity for the complete removal of residual microcalcifications after neoadjuvant chemotherapy for breast cancer.

Lee Jeeyeon J Park Nora Jee-Young NJ Park Ho Yong HY Kim Wan Wook WW Kang Byeongju B Keum Heejung H Kim Hye Jung HJ Kim Won Hwa WH Chae Yee Soo YS Lee Soo Jung SJ Lee In Hee IH Park Ji-Young JY Jung Jin Hyang JH

Scientific reports 20221213 1

The surgical range of breast cancer that shows pathologic complete response (pCR) without change in microcalcifications after neoadjuvant chemotherapy (NAC) is controversial. This study examined whole breast specimens to evaluate the necessity of mastectomy in those cases. The viability of cancer cells around the residual microcalcification was assessed using prospectively collected breast samples to confirm the presence or absence of cancer cells. A total of 144 patients with breast cancer and ...[more]

PMID: 36513704

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Project description:The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-Pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports of 100 cases from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists. The size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis, and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-Pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among pathologists was 0.931 (95% confidence interval (CI) 0.908-0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% CI 0.539-0.626). The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient=0.980; 95% CI 0.954-0.992), than the primary component (overall concordance correlation coefficient=0.795; 95% CI 0.716-0.853). At a median follow-up of 12 years residual cancer burden determined by each of the pathologists had the same prognostic accuracy for distant recurrence-free and survival (overall concordance correlation coefficient=0.995; 95% CI 0.989-0.998). Residual cancer burden assessment is highly reproducible, with reproducible long-term prognostic significance.

Project description:BackgroundResidual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC.MethodsA total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC.ResultsThere were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486).ConclusionsRegardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Project description:ImportanceImage-guided breast biopsy of a residual imaging abnormality or tumor bed after neoadjuvant chemotherapy (NACT) is increasingly used to assess residual cancer, facilitate risk-adaptive surgery, and potentially identify exceptional responders in whom local therapy may be de-escalated.ObjectiveTo further assess the accuracy of post-NACT image-guided biopsy to predict residual cancer in the breast.Design, setting, and participantsThis diagnostic study analyzed multicenter patient-level data of patients with breast cancer who were treated with NACT and underwent image-guided biopsy before surgery at Royal Marsden Hospital in London, UK; Seoul National University Hospital in Seoul, South Korea; and MD Anderson Cancer Center in Houston, Texas. Data were analyzed from June to July 2019.Main outcomes and measuresDiagnostic accuracy of post-NACT image-guided biopsy. Final surgical pathology was used as reference standard.ResultsData from 166 women were analyzed. The median (range) age was 49 (25-76) years. The median (range) tumor size on pretreatment and posttreatment imaging was 33.5 (12-100) mm and 10 (0-100) mm, respectively. The overall pathologic complete response rate was 51.2% (n = 85) (16.1% [5 of 31] for hormone receptor-positive/ERBB2 (formerly HER2)-negative; 44.7% [21 of 47] for hormone receptor-positive/ERBB2-positive; 69% [20 of 29] for hormone receptor-negative/ERBB2-positive; and 66.1% [39 of 59] for triple negative). The majority (143 [86.1%]) underwent image-guided vacuum-assisted biopsy (VAB), and 23 had core-cut biopsy. The median (range) needle gauge was 10 (7-14), and the median (range) number of samples was 6 (2-18). When image-guided biopsy (VAB and core-cut biopsy) was representative (159 [95.8%]), the false-negative rate across the whole cohort was 18.7% (95% CI, 10.6%-29.3%). Subgroup analysis of patients with a complete/partial clinical response and residual imaging abnormality of 2 cm or smaller with at least 6 VABs taken (76 [45.8%]) demonstrated a false-negative rate of 3.2% (95% CI, 0.1%-16.7%), a negative predictive value of 97.4% (95% CI, 86.5%-99.9%), and an overall accuracy of 89.5% (95% CI, 80.3%-95.3%).Conclusions and relevanceThis large multicenter pooled data analysis suggests that a standardized protocol using image-guided VAB of a tumor bed measuring 2 cm or smaller with 6 or more representative samples allows reliable prediction of residual disease. These results could inform the design of de-escalation trials in NACT exceptional responders testing the safety of eliminating surgery.

Project description:BackgroundThe persistence of residual tumour after neoadjuvant chemotherapy (NAC) in localised triple-negative breast cancer (TNBC) is known to have a negative prognostic value. However, different degrees of expression of some immunohistochemical markers may correlate with different prognoses.MethodsThe expression of biomarkers with a known prognostic value, i.e., cytokeratin 5/6 (CK5/6), androgen receptor (AR), epidermal growth factor receptor (EGFR) proliferation-related nuclear antigen Ki-67, human epidermal growth factor receptor 2 (HER2), protein 53 (p53), forkhead box protein 3 (FOXP3), and cluster differentiation 8 (CD8), was analysed by immunohistochemistry in 111 samples after NAC in non-metastatic TNBC patients addressed to Georges-François Leclerc Cancer Centre Dijon, France. Clinical and pathological variables were retrospectively collected. Cox regression was used to identify immunohistochemical (IHC) and clinicopathological predictors of event-free survival (EFS) (relapse or death).ResultsMedian age was 50.4 years (range 25.6-88.3), 55.9% (n = 62) were non-menopausal, 70 (63.1%) had stage IIA-IIB disease. NAC was mostly sequential anthracycline-taxanes (72.1%), and surgical intervention was principally conservative (51.3%). We found 65.7% ypT1, 47.2% lymph node involvement (ypN+), and 29.4% lymphovascular invasion (LVI). Most residual tumours were EGFR >110 (H-score) (60.5%, n = 66), AR ≥4% (53.2%, n = 58), p53-positive mutated (52.7%, n = 58), CD8 ≥26 (58.1%, n = 61), FOXP3 ≥7 (51.4%, n = 54), more than half in the stroma, and 52.3% (n = 58) HER2 score 0. After a median follow-up of 80.8 months, 48.6% had relapsed. Median EFS was 62.3 months (95% CI, 37.2-not reached (NR)). Factors independently associated with poor EFS were AR-low (p = 0.002), ypN+ (p < 0.001), and LVI (p = 0.001). Factors associated with lower overall survival (OS) were EGFR-low (p = 0.041), Ki-67 high (p = 0.024), and ypN+ (p < 0.001).ConclusionPost-NAC residual disease in TNBC showed biomarkers specific to a basal-like subtype and markers of lymphocyte infiltration mostly present in the stroma. Prognostic markers for EFS were AR, LVI, and ypN and warrant further validation in a prognostic model.

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Oncologic necessity for the complete removal of residual microcalcifications after neoadjuvant chemotherapy for breast cancer.

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Oncologic necessity for the complete removal of residual microcalcifications after neoadjuvant chemotherapy for breast cancer.

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