Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer

Pastorello, Ricardo; Laws, Alison; Grossmith, Samantha; King, Claire; McGrath, Monica; Mittendorf, Elizabeth A.; King, Tari A.; Schnitt, Stuart J.

doi:10.1038/s41379-020-00714-5

Cited by 22 publications

(16 citation statements)

References 21 publications

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“…This finding is also pathologically validated by a recent study showing that a circumscribed pattern of the residual tumor after NAC was more frequent in HR− tumors and a scattered pattern of response was much more frequent in the HR+ tumors. Triple negative and HER2+ tumors are more often high grade compared to HR+ tumors, and a scattered pattern was more frequent among grade 1 or 2 than among grade 3 tumors 18 . Further, high grade cancers show higher proliferation and are thereby inherently more sensitive to NAC.…”

Section: Discussionmentioning

confidence: 93%

MRI to assess response after neoadjuvant chemotherapy in breast cancer subtypes: a systematic review and meta-analysis

et al. 2022

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This meta-analysis aimed to estimate and compare sensitivity, specificity, positive- (PPV) and negative predictive value (NPV) of magnetic resonance imaging (MRI) for predicting pathological complete remission (pCR) after neoadjuvant chemotherapy (NAC) in patients with early-stage breast cancer. We stratified for molecular subtype by immunohistochemistry (IHC) and explored the impact of other factors. Two researchers systematically searched PUBMED and EMBASE to select relevant studies and extract data. For meta-analysis of sensitivity and specificity, we used bivariate random-effects models. Twenty-six included studies contained 4497 patients. There was a significant impact of IHC subtype on post-NAC MRI accuracy (p = 0.0082) for pCR. The pooled sensitivity was 0.67 [95% CI 0.58–0.74] for the HR−/HER2−, 0.65 [95% CI 0.56–0.73] for the HR−/HER2+, 0.55 [95% CI 0.45–0.64] for the HR+/HER2− and 0.60 [95% CI 0.50–0.70] for the HR+/HER2+ subtype. The pooled specificity was 0.85 [95% CI 0.81–0.88] for the HR−/HER2−, 0.81 [95% CI 0.74–0.86] for the HR−/HER2+, 0.88[95% CI 0.84–0.91] for the HR+/HER2− and 0.74 [95% CI 0.63–0.83] for the HR+/HER2+ subtype. The PPV was highest in the HR-/HER2- subtype and lowest in the HR+/HER2− subtype. MRI field strength of 3.0 T was associated with a higher sensitivity compared to 1.5 T (p = 0.00063). The accuracy of MRI for predicting pCR depends on molecular subtype, which should be taken into account in clinical practice. Higher MRI field strength positively impacts accuracy. When intervention trials based on MRI response evaluation are designed, the impact of IHC subtype and field strength on MR accuracy should be considered.

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Section: Discussionmentioning

confidence: 93%

MRI to assess response after neoadjuvant chemotherapy in breast cancer subtypes: a systematic review and meta-analysis

et al. 2022

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“…In addition, the saved high-quality slides can be used to for future analysis, for example, artificial intelligence-assisted interpretation of indicators such as TILs. Investigations have shown that the tumor regression grade of post-NAT breast cancer [ 27 ] is significantly correlated with prognosis, and the emergence of large sections can assist physicians in better evaluating these crucial pathological features. Furthermore, the construction of a WSI database for the patient’s tumor bed can facilitate the easy extraction of saved high-quality large sections of the tumor bed, which can be compared with H&E slides from preoperative needle biopsy, and possible recurrent or metastatic lesions in the future.…”

Section: Discussionmentioning

confidence: 99%

Reconstructing virtual large slides can improve the accuracy and consistency of tumor bed evaluation for breast cancer after neoadjuvant therapy

et al. 2022

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Background To explore whether the “WSI Stitcher”, a program we developed for reconstructing virtual large slide through whole slide imaging fragments stitching, can improve the efficiency and consistency of pathologists in evaluating the tumor bed after neoadjuvant treatment of breast cancer compared with the conventional methods through stack splicing of physical slides. Methods This study analyzed the advantages of using software-assisted methods to evaluate the tumor bed after neoadjuvant treatment of breast cancer. This new method is to use “WSI Stitcher” to stitch all the WSI fragments together to reconstruct a virtual large slide and evaluate the tumor bed with the help of the built-in ruler and tumor proportion calculation functions. Results Compared with the conventional method, the evaluation time of the software-assisted method was shortened by 35%(P < 0.001). In the process of tumor bed assessment after neoadjuvant treatment of breast cancer, the software-assisted method has higher intraclass correlation coefficient when measuring the length (0.994 versus 0.934), width (0.992 versus 0.927), percentage of residual tumor cells (0.947 versus 0.878), percentage of carcinoma in situ (0.983 versus 0.881) and RCB index(0.997 versus 0.772). The software-assisted method has higher kappa values when evaluating tumor staging(0.901 versus 0.687) and RCB grading (0.963 versus 0.857). Conclusion The “WSI Stitcher” is an effective tool to help pathologists with the assessment of breast cancer after neoadjuvant treatment.

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“…Perhaps unsurprisingly, the pattern of response has been shown to correlate with molecular subtype. In one series looking at histological findings, TNBC was more likely to show the concentric shrinking pattern, whilst ER+/HER2-and HER2+ tumours more commonly showed the scatter pat-tern of response (53%, versus 11% and 29% respectively) (83). On closer analysis, the HER2+ tumours differed by ER status, with 78% of ER+/ HER2+ tumours showing the scatter pattern compared with 53% of ER-/HER2+ cancers.…”

Section: A B Cmentioning

confidence: 99%

Neoadjuvant Chemotherapy for Breast Cancer: Moving Beyond Pathological Complete Response in the Molecular Age

Provenzano

2021

ama

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This review focuses on neoadjuvant chemotherapy for breast cancer which introduces practical issues for pathologists, including predicting response, optimising specimen handling, size measurement and assessment of residual disease, and recent advances in management of the axilla. The role of neoadjuvant chemotherapy in breast cancer is increasing, and it has become standard of care for high risk Human Epidermal Growth Factor Receptor 2 positive and triple negative breast cancers. The benefits of the neoadjuvant approach extend beyond pathological complete response to tumour downstaging permitting conservative surgi- cal options in the breast and axilla, and assessment of response provides valuable prognostic information to enable escalation and de-escalation of adjuvant therapy to optimise oncological outcomes. Hence histopathologists play a vital role in patient management in the neoadjuvant setting. Optimal patient selection for neoadjuvant chemotherapy requires consideration of pre- treatment histopathological and molecular tumour characteristics. Post chemotherapy, tumour staging can be challenging, and changes in criteria for measurement of primary tumour and metastases in the 7th and 8th editions of the TNM have led to confu- sion amongst pathologists. This review offers practical guidance on specimen handling and measurement of lesion size. Mov- ing forwards more detailed information on degree of response will be required for adjuvant therapy decision making, and the Residual Cancer Burden is emerging as the preferred method for quantifying residual disease not just within clinical trials but in routine practice. Recent advances in management of the axilla are discussed, including the significance of minimal residual disease in the form of isolated tumour cells and micrometastases which portend a worse prognosis in the neoadjuvant setting.Conclusion. Neoadjuvant chemotherapy now forms part of routine breast cancer management, and detailed histopathological assessment and an understanding of the importance of molecular tumour biology is essential for clinical decision making.

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Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer

Cited by 22 publications

References 21 publications

MRI to assess response after neoadjuvant chemotherapy in breast cancer subtypes: a systematic review and meta-analysis

MRI to assess response after neoadjuvant chemotherapy in breast cancer subtypes: a systematic review and meta-analysis

Reconstructing virtual large slides can improve the accuracy and consistency of tumor bed evaluation for breast cancer after neoadjuvant therapy

Neoadjuvant Chemotherapy for Breast Cancer: Moving Beyond Pathological Complete Response in the Molecular Age

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