Pathological complete response to neoadjuvant systemic therapy in 789 early and locally advanced breast cancer patients: The Royal Marsden experience

Battisti, Nicolò Matteo Luca; True, V; Chaabouni, Narda; Chopra, Neha; Lee, Karla; Shepherd, Scott T.C.; Shapira-Rotenberg, Tal; Joshi, Rashi; McGrath, Sophie; Okines, Alicia; Parton, Marina; Turner, Nicholas C.; Mohammed, Kabir; Allen, Mark; Johnston, Stephen; Ring, Alistair

doi:10.1007/s10549-019-05444-0

Cited by 22 publications

(20 citation statements)

References 17 publications

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“…Pathological complete response (pCR) is the complete eradication of the tumour following the NACT treatment regimen. While studies have shown that pCR is associated with improved survival, this varies according to clinicopathological features and molecular subtype [ 1 , 2 ]. It has recently been reported that only 19.2% of patients will achieve a pCR [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Prospective Assessment of Systemic MicroRNAs as Markers of Response to Neoadjuvant Chemotherapy in Breast Cancer

McGuire

Casey

Waldron

et al. 2020

Cancers

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Neoadjuvant chemotherapy (NACT) is used in locally advanced breast cancer to reduce tumour burden prior to surgical resection. However, only a subset of NACT treated patients will respond to treatment or achieve a pathologic complete response (pCR). This multicenter, prospective study (CTRIAL-IE (ICORG) 10-11 study) evaluated circulating microRNA as novel non-invasive prognostic biomarkers of NACT response in breast cancer. Selected circulating microRNAs (Let-7a, miR-21, miR-145, miR-155, miR-195) were quantified from patients undergoing standard of care NACT treatment (n = 114) from whole blood at collected at diagnosis, and the association with NACT response and clinicopathological features evaluated. NACT responders had significantly lower levels of miR-21 (p = 0.036) and miR-195 (p = 0.017), compared to non-responders. Evaluating all breast cancer cases miR-21 was found to be an independent predictor of response (OR 0.538, 95% CI 0.308–0.943, p < 0.05). Luminal cancer NACT responders were found to have significantly decreased levels of miR-145 (p = 0.033) and miR-21 (p = 0.048), compared to non-responders. This study demonstrates the prognostic ability of miR-21, miR-195 and miR-145 as circulating biomarkers stratifying breast cancer patients by NACT response, identifying patients that will derive the maximum benefit from chemotherapy.

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Section: Introductionmentioning

confidence: 99%

“…Response to NACT has been shown to vary by breast cancer subtype, tumour grade and stage, with the highest complete response rates in the HER2+ (non-luminal) subtype [ 1 , 2 , 3 ]. Subtype specific therapy, such as trastuzumab, significantly increases the pCR rates in HER2 receptor positive breast cancers [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Prospective Assessment of Systemic MicroRNAs as Markers of Response to Neoadjuvant Chemotherapy in Breast Cancer

McGuire

Casey

Waldron

et al. 2020

Cancers

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“…Our results reveal a higher portion of NACT use in university hospitals, especially for HRþ HER2À cases, which might be one explanation for their lower overall pCR rate. In this context the importance of NACT used for in vivo sensitivity testing and providing postneoadjuvant therapy escalation in cases of non-pCR must be considered [35]. Until now, there has been no comparable analysis between different hospital types for the systematic treatment of EBC patients regarding chemotherapy use and pCR rates after NACT in Germany.…”

Section: Discussionmentioning

confidence: 99%

Do hospital type or caseload make a difference in chemotherapy treatment patterns for early breast cancer? Results from 104 German institutions, 2008–2017

et al. 2021

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Background: Over the past decade, chemotherapy has been used more selectively in early breast cancer (EBC) due to better risk stratification. Neoadjuvant chemotherapy (NACT) has evolved to the primary treatment option. The type and size of hospitals is known to have a substantial influence on the kinds of treatment they provide, and therefore on patient outcomes (e.g. rates for pathological complete response, pCR), but it is not yet known how this has affected delivery of chemotherapy for EBC in Germany. Methods: This study analyzed chemotherapy use and pCR rates after NACT for EBC patients treated at 104 German institutions 2008e2017. Institutions were separated into associated hospital type (university hospital; teaching hospital; community hospital) and annual caseload ( 100; 101e250; >250 cases/ year). Results: Overall, 124,084 patients were included, of whom 11.6% were treated at university hospitals, 63.1% at teaching hospitals, and 25.3% at community hospitals. In total, 46,274 (37.3%) received chemotherapy, of whom 44,765 had information available about systemic treatment and surgery. From 2008 to 2017, chemotherapy use declined from 48.3% to 36.4% for university hospitals, from 40.7% to 30.3% for teaching hospitals, and from 42.4% to 33.7% for community hospitals. Furthermore, the proportion of NACT increased the most in university hospitals (from 32.0% to 68.1%); whereas, the rate of pCR (defined as ypT0 ypN0) increased irrespective of institutional type. Analyses regarding annual caseload did not show any differences. Conclusions: The results from this large, nationwide cohort reflect a more selective use of chemotherapy in Germany, irrespective of institutional type or case load.

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“…The variables selected by us for risk scoring were those which were retained as significant factors in multivariate modelling and have been reported as important prognostic factors for breast cancer in many studies [4][5][6]. Even though grade was not significant on univariate analysis, we incorporated it because it is a proven prognostic factor for predicting recurrence risk in BC [7]. The poor prognosis of young women with breast cancer is well known and also emerged as a significant prognostic factor in our population [5] While data from the west report only 9% women with BC under 35 years age, our population comprised of 30% women under 40 years, thereby leading to higher recurrence risk [7].…”

Section: Discussionmentioning

confidence: 99%

“…Even though grade was not significant on univariate analysis, we incorporated it because it is a proven prognostic factor for predicting recurrence risk in BC [7]. The poor prognosis of young women with breast cancer is well known and also emerged as a significant prognostic factor in our population [5] While data from the west report only 9% women with BC under 35 years age, our population comprised of 30% women under 40 years, thereby leading to higher recurrence risk [7]. As expected, the higher T and N status were associated with higher recurrence risk, consistent with other predictive models and a large number of studies [8].…”

Section: Discussionmentioning

confidence: 99%

A Simple Risk Scoring System for Predicting Recurrence in Women with Locally Advanced Breast Cancer (LABC) Treated with Neoadjuvant Chemotherapy (NACT)

Agrawal

Mishra

et al. 2021

JAMMR

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Introduction: Breast cancer commonly presents in locally advanced stage (LABC) in developing countries, for which NACT followed by surgery and radiotherapy is the standard of care. There is a need for a simple tool to risk categorise patients in the clinic, so that treatment intensification can be offered to women with high risk of recurrence. Materials and Methods: Data of prospectively maintained database of LABC (between January 2007 - December 2012), who received NACT followed by surgery, radiotherapy and endocrine therapy was retrospectively analysed for clinico-pathological factors associated with disease recurrences. A recurrence risk scoring model was developed on the basis of regression coefficient of identified independent risk factors. Results: In the data set of 206 patients, the median follow-up was 48 months (range: 6-156 months) and mean and median disease-free survival (DFS) were 87.41 and 85 months. The 1, 5, 10 years DFS was 95%, 54% and 41%. The independent risk factors (on modified p value <0.40) for recurrence were Tumour stage, Nodes stage, grade, age groups, pathologic complete response, intrinsic subtype, and type of surgery. Risk score prepared by regression coefficient (β), was in the range of 1-8 with median score of 5. ROC curve showed that area under ROC Curve of the score was 71.8% (95% CI: 64.8%-78.8%, p<0.001). To detect recurrences, a risk score ≥3 had at least 93.1% sensitivity and 31.9% specificity whereas score ≥4 had at least 73.5% sensitivity and 59.6% specificity. Based on cluster analysis, score 1-4 was identified as low risk whereas 5-6 as moderate risk group and ≥7 identified as high-risk group and their mean/median disease free survival time were 107.86/ NR, 66.99/30 months and 58.34/20 months respectively. Conclusions: The significant difference in DFS among three risk groups, indicates goodness of the fit of our risk score model. The risk scoring model developed by us is simple, easy to use in clinic and can be used for selecting high risk patients who benefit from treatment intensification.

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Pathological complete response to neoadjuvant systemic therapy in 789 early and locally advanced breast cancer patients: The Royal Marsden experience

Cited by 22 publications

References 17 publications

Prospective Assessment of Systemic MicroRNAs as Markers of Response to Neoadjuvant Chemotherapy in Breast Cancer

Prospective Assessment of Systemic MicroRNAs as Markers of Response to Neoadjuvant Chemotherapy in Breast Cancer

Do hospital type or caseload make a difference in chemotherapy treatment patterns for early breast cancer? Results from 104 German institutions, 2008–2017

A Simple Risk Scoring System for Predicting Recurrence in Women with Locally Advanced Breast Cancer (LABC) Treated with Neoadjuvant Chemotherapy (NACT)

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