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http://orcid.org/0000-0003-3490-3702
Abstract
Abstract
Background: In Finland, breast cancers treated with neoadjuvant chemotherapy (NACT) are usually locally advanced and/or have an inflammatory phenotype. We evaluated early NACT responses in breast tumours and lymph nodes and their correlation with survival.
Material and methods: We collected a retrospective dataset of 145 patients with very high-risk but non-metastasised breast cancers that were treated with NACT in a Finnish University Hospital between September 2013 and January 2019. The patients underwent magnetic resonance imaging (MRI) scans before beginning NACT and after every second NACT cycle thereafter.
Results: The total pathological complete response rate was only 10.7% and breast cancer-specific survival (BCSS) at 24 months was 93.0%. The 2-year breast cancer-specific survival (BCSS) rate was 93.0%, but this varied from 86.5% for the triple-negative subtype to 100.0% for the luminal A-like subtype. Enlargement of the malignant axillary lymph nodes during the first two NACT cycles was associated with poor BCSS rates in HER2-negative patients (p = .00003 in the univariate analysis; hazard ratio = 26.3; 95% confidence interval = 2.66–259.6; p = .005 in the multivariate analysis). Furthermore, progression in the combined diameters of the breast tumours and axillary lymph nodes during the period between a patient’s pre-treatment MRI and her MRI after two NACT cycles was also correlated with worse BCSS rates in both univariate and multivariate analyses.
Conclusions: An early MRI assessment after two NACT cycles, specifically of the tumour’s axillary lymph nodes, has the potential to predict short-term BCSS in patients with locally advanced HER2-negative breast cancers.
Background
In most countries, neoadjuvant chemotherapy (NACT) is increasingly used as a replacement for adjuvant chemotherapy in patients with operable breast cancer, and especially for those with the most aggressive subtypes [1]. However, recent Finnish breast cancer guidelines still recommend using NACT only in patients that are considered primarily inoperable due to inflammatory or widely locally advanced breast cancer [2]. Locally advanced breast cancers typically have an aggressive biological profile as well as adverse TNM prognostic factors, and their overall prognosis is poor [3].
The best-characterised prognostic factor for breast cancer patients treated with NACT is the achievement of pathological complete response (pCR), i.e., the achievement of ypT0N0 staging, indicating that no residual cancer (including carcinoma in situ) is present in either the breast or lymph nodes [4,5]. Although other prognostic factors exist, their relevance may vary by subtype [6]. Moreover, while an early radiological response during NACT can predict pCR, its effect on survival is unclear, and even less is known about the prognostic significance of early responses when lymph nodes are evaluated separately [7].
Given these gaps in current research, in the present study, we analysed a retrospective dataset of patients with locally advanced or inflammatory breast cancers treated with NACT. We evaluated the correlation between early primary tumour or lymph node responses and breast cancer-specific survival (BCSS) in this high-risk group. We also investigated whether there were correlations among breast cancer subtypes and BCSS rates.
Material and methods
The study population consisted of 145 consecutive female breast cancer patients treated with NACT who also received follow-up magnetic resonance imaging (MRI) scans at Oulu University Hospital between September 2013 and January 2019. Each decision to use NACT was evaluated individually in a multidisciplinary meeting at the University Hospital, with the main criteria being locally advanced or inflammatory breast cancer. All clinical data used in this study were collected retrospectively from the Oulu University Hospital archives (Table 1).
Table 1. Patient characteristics and treatment.
Only patients with no distant metastases at the time of diagnosis were included in the study. Distant metastases were excluded using bone scans, abdominal ultrasounds and computerised tomography scans of the thorax and/or abdomen. Before a patient began NACT, her tumour histopathology was defined using core needle biopsy samples and axillary lymph node involvement was confirmed with fine needle aspiration samples.
Immunohistochemical scoring was determined using the core needle samples from the patients’ pathological diagnoses. The expression levels of nuclear Ki-67 and the oestrogen receptors (ER) and progesterone receptors (PR) were analysed as described in Karihtala et al. [8]. Tumour samples were considered receptor-positive if nuclear ER or PR were expressed in more than 1% of the invasive tumour cells. HER2 overexpression was assessed using immunohistochemistry. HER2-positive results were confirmed using chromogenic in situ hybridisation to determine their gene amplification status; tumours with ≥6 copies of the gene were considered HER2-positive [9]. Each patient’s histopathological grade and subtype and primarily preoperative core needle sample data were also included, in conjunction with their hormone receptor and Ki-67 status, and their information was completed with posttreatment data when applicable. Preoperative data were used to establish a patient’s HER2 status, except for in two cases in which a patient’s HER2 status was negative in core needle samples before NACT but positive after NACT; these cases were classed as HER2-positive in our analyses.
Tumours were classed into five intrinsic subtypes according to the ESMO Early Breast Cancer Clinical Practice Guidelines [10], which were briefly defined as follows. Luminal A-like carcinomas expressed both ER and PR, but HER2 was not overexpressed and Ki-67 was expressed in <15% of their cells. Luminal B-like (HER2-negative) carcinomas were also ER positive and HER2-negative, but they either showed Ki-67 expression in >15% of their cells or were PR negative. Luminal B-like (HER2-positive) carcinomas still expressed ER, but they also overexpressed HER2. Triple-negative breast cancers (TNBC) were defined as tumours with no expression of ER, PR or HER2. HER2-positive (non-luminal) tumours overexpressed HER2 but did not express either ER or PR.
Treatment
Chemotherapy was administered according to the guidelines of the Finnish Breast Cancer Group and our own institutional guidelines. Most patients received 8 cycles of docetaxel and doxorubicin as their NACT, and all patients received a minimum of 2 NACT cycles (range 2–12, median 8; Table 1). All patients with HER2-positive breast cancer received trastutzumab ± pertuzumab as both neoadjuvant and adjuvant therapy. Chemotherapy was altered or terminated if the patient suffered from severe adverse effects. Treatment was also re-evaluated in the case of tumour progression or poor response to NACT. All patients also underwent a mastectomy; the axillary procedure was either axillary lymph node dissection (n = 139) or sentinel lymph node biopsy (n = 6). After surgery, 142 patients (97.9%) received loco-regional radiotherapy, 101 patients (69.7%) received endocrine therapy, 41 patients (28.3%) received adjuvant trastuzumab and 14 (9.7%) received adjuvant chemotherapy (Table 1). Either conventional or hypofractionated radiotherapy could be used.
MRI scans
Each patient’s radiological treatment response was monitored with an MRI scan after every two cycles of NACT, which is standard procedure in our hospital. MRI scans were performed in either 1.5 T or 3.0 T MRI scanners with dedicated breast coils. The imaging protocol included dynamic contrast-enhanced fat-saturated (DCE) T1 and T2 images. All MRI scans were evaluated by one breast radiologist with 6 years of experience performing breast MRI scans who was blinded to the final pathologic treatment outcome.
Evaluations of patient responses to NACT
Patient responses to NACT were evaluated using 3-D DCE MRI images. The maximum diameter of the enhancing breast lesion was measured from the axial, sagittal or coronal plane; both mass and non-mass lesions were included. Axillary lymph nodes were assessed in the MRI evaluations if the patient’s cytology indicated metastasis in the axilla; otherwise, the axilla’s negative status was confirmed by radiology. Lymph nodes were evaluated by measuring each lymph node’s short axis and/or abnormal (>3 mm) cortex thickening in the DCE MRI images. Early response to treatment was defined as the change in the maximum diameter of the enhancing target lesions between the pre-treatment MRI and the MRI after the first two NACT cycles. Final radiological response was defined as the change in the maximum diameter of the enhancing lesion between the pre-treatment and pre-surgery MRI examinations. Due to changing procedures in the treatment centre, pre-surgery (i.e., after the conclusion of all NACT cycles) MRI scans were only performed for 79 patients (54.5%); therefore, only these images were used for pre-surgery MRI accuracy analyses.
Changes to the malignant axillary lymph nodes and primary breast tumours were analysed both separately and as a sum of all lymph node and primary tumour target lesion diameters. Progression was defined as any increase in the diameter of the target lesions; non-progression was defined as either a decrease or non-detectable change in the target lesions. Partial radiological response was defined according to the Response evaluation criteria in solid tumours (RECIST) criteria of at least a 30% decrease in the diameter of the target lesion as compared with baseline diameter [11]. Complete radiological response (rCR) was defined as the disappearance of the enhancing lesion in the pre-surgery MRI scan. A pathologist determined the final pathological response from the surgical breast specimens; complete pathological response (pCR) was defined as the disappearance of all invasive and in situ tumour cells from the breast and axillary lymph nodes (ypT0N0).
Statistical analyses
Statistical analyses were conducted using SPSS version 25.0.0.0 for Mac (IBM Corporation, Armonk, NY, USA). Survival were analysed using the Kaplan–Meier method and the log-rank test. BCSS was defined as the time between diagnosis and confirmed death due to breast cancer. Patients with bilateral breast cancer or earlier breast cancer were excluded from the survival analyses. Multivariate analyses were conducted using the Cox regression method. The number of malignant lymph nodes was included to the multivariate analysis and it was treated as a continuous variable. p-values <.05 were considered significant.
Ethics approval
This study was approved by the Local Ethics Committee of the Ostrobothnia Hospital District (114/2011, amendment 23.2.2015) and the National Supervisory Authority for Welfare and Health (1339/05.01.00.06/2009).
Results
Mean patient age at diagnosis was 55.2 years (range 23–80). The follow-up time was defined as the time between a patient’s first diagnostic biopsy and either the last date when the patient was known to be alive or the time her death. Mean follow-up time was 25 months (median 22.7, range 2.1–79.3).
During follow-up, distant metastases presented in 23 patients (15.9%) and local relapses occurred in 8 patients (5.5%). Mean disease-free time before local relapse was 18.6 months (range 6.4–34.2) and mean disease-free time before distant metastases was 17.3 months (range 7.2–32.3). Tumour characteristics before and after NACT are presented in Tables 2 and 3.
Table 2. Pre-treatment tumour characteristics.
Table 3. Post-treatment tumour characteristics.
Prior to beginning NACT, 77.9% of tumours were classed as T3 or T4 and 14.5% of patients had inflammatory breast cancer. The early radiological responses to NACT, using the RECIST criteria in DCE MRI scans after two NACT cycles, were 2 complete responses (1.4%), 29 partial responses (20.0%), 106 stable disease cases (73.1%) and one progressive disease case (0.7%), with 7 missing cases (4.8%). Among the 79 patients for whom final pre-surgery radiological responses were available, there were 6 complete responses (7.6%), 36 partial responses (45.6%), 34 stable disease cases (43.0%) and 3 progressive disease cases (3.8%). Early increases occurred in 25 cases (17.2%) for breast tumour diameter and in 10 cases (6.9%) for axillary lymph nodes. Luminal A-like tumours were the only subtype that did not show any pCR (Table 4). Three patients had progressive disease during NACT, of whom two had TNBC subtype. Lobular and ductal carcinomas did not show difference in responses (p = .19).
Table 4. Distribution of final breast tumour responses and axillary lymph node responses after neoadjuvant chemotherapy, according to breast cancer subtype.
Survival
Early lymph node responses
A total of nine patients without previous breast cancer and without bilateral breast cancer had early progression in their axillary lymph nodes. Five of them had HER2-negative breast cancer and four had HER2-positive breast cancer. Early disease progression (i.e., progression between a patient’s pre-treatment MRI and her MRI after two NACT cycles) of the axillary lymph nodes was associated with poor BCSS in HER2-negative patients (log-rank p = .00003). In a multivariate analysis of early axillary lymph node progression alongside the number of malignant axillary lymph nodes, early lymph node progression remained statistically significant (hazard ratio [HR] = 26.3; 95% confidence interval [CI] = 2.66–259.6; p = .005; for number of malignant axillary lymph nodes, HR = 1.09, 95% CI = 0.92–1.30, p = .34; Figure 1(A)). Notably, this association was not observed in HER2-positive patients.
Published online:
12 May 2020Figure 1. Magnetic resonance imaging response observed after two cycles of neoadjuvant chemotherapy, (A) in malignant lymph nodes, (B) in primary tumour(s) and (C) in all target lesions. Although all subtypes were associated with poor breast cancer–specific survival, (D) shows the differences in subtype-specific outcomes. The x-axis has been cut from the third quartile (37.5 months) in figures.
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Figure 1. Magnetic resonance imaging response observed after two cycles of neoadjuvant chemotherapy, (A) in malignant lymph nodes, (B) in primary tumour(s) and (C) in all target lesions. Although all subtypes were associated with poor breast cancer–specific survival, (D) shows the differences in subtype-specific outcomes. The x-axis has been cut from the third quartile (37.5 months) in figures.
Early breast tumour responses
Partial early responses [11] in breast tumours were associated with better BCSS (log-rank p = .036), although this association was not significant in the multivariate analysis. There were no breast cancer-related deaths during the follow-up period among patients with an early partial response in breast tumours (Figure 1(B)).
Early responses in both breast and lymph node target lesions
Early disease progression in the sum of all target lesions (i.e., the combined diameters of both breast tumours and axillary lymph nodes) was negatively correlated with BCSS (log-rank p = .055; Figure 1(C). This association was significant in the multivariate analysis (HR = 4.8, 95% CI = 1.3–17.5, p = .007; for the number of malignant axillary lymph nodes, HR = 1.1, 95% CI = 1.0–1.2, p = .007).
Breast cancer-specific survival
BCSS at 24 months for the cohort as a whole was 92.5% regardless of the in- or exclusion of patients with bilateral and prior breast cancer. BCSS for patients with different molecular subtypes of breast cancer are presented in Figure 1(D). No breast cancer-related deaths were observed in patients with the luminal A-like subtype. BCSS at 24 months was also 100% for the luminal B-like (HER2-positive) subtype, 87.2% for the luminal B-like (HER2-negative) subtype, 100.0% for the HER2 overexpression subtype and 86.5% for the TNBC subtype.
Discussion
To the best of our knowledge, no previous studies have specifically evaluated the early progression of breast cancer lymph node metastases during NACT as a possible prognostic factor. As the main result, we report in this retrospective, single-centre study poorer outcome in HER2-negative patients, who had progression in lymph nodes already in the very beginning of the NACT. However, due to the low number of patients and events, these results can be considered as hypothesis generating.
NACT is increasingly common, especially for TNBC and HER2-positive tumour subtypes. The NACT approach has several advantages compared to adjuvant chemotherapy, including the ability to measure a tumour’s in vivo response or resistance to any given therapy [10]. In theory, tailoring a patient’s treatment to their specific tumour after its early progression not only enables the possibility of changing treatment methods to a potentially more effective one but may also allow a patient to avoid unnecessary toxicity and costs. However, the current guidelines of the Finnish Breast Cancer Group recommend limiting NACT’s use to patients with locally advanced or inflammatory breast cancer [2].
There is mounting evidence that several MRI methods can predict pCR early in the treatment course (reviewed in Taourel et al. [12]). For instance, one study found that functional tumour volume, as assessed by a semi-automated computer analysis based on the signal enhancement ratio, was a better predictor after even just one NACT cycle of a patient’s likelihood of pCR than the change in a patient’s tumour diameter [13]. A meta-analysis of six studies also concluded that the mean apparent diffusion coefficient in diffusion-weighted MRI scans of breast tumours after one NACT cycle was also a strong predictor of a patient’s eventual pCR [14]. However, all of these studies specifically evaluated tumours’ radiological responses to treatment and primarily concentrated on changes in the primary tumour, while our aim in the present study was to establish a correlation between early primary tumour or lymph node responses and BCSS. Since pCR is a strong predictor of survival in breast cancer NACT, our results are consistent with those found in previous studies despite the previous studies have mainly concentrated on the changes of the primary tumour [5].
A recent retrospective study concluded that breast rCR and pCR were poor predictors of axillary response [15]; however, this may also depend on the specific breast cancer subtype [16,17]. To the best of our knowledge, no previous studies have specifically investigated the role of early lymph node progression during NACT for breast cancer or any other cancer. In the current study, the radiological progression of the axillary lymph nodes after two NACT cycles was an even stronger predictor of poor BCSS the absolute number of postoperatively identified malignant axillary lymph nodes. In addition to depicting aggressive and chemoresistant nature of breast cancer in general, it is possible that early progression in lymph nodes is indicative to cancer’s tendency to send distant metastases. In general, HER2-positive patients have better responses to NACT, and they may also receive targeted treatment as second-line NACT, while HER2-negative patients only have other chemotherapy options available. This, along with the small number of HER2-positive cases in our study, may explain why early lymph node progression predicted such poor outcomes only among HER2-negative patients. Although early disease progression in the axillary lymph nodes was only rarely observed in HER2-negative patients, it has the potential to be an easily accessible and inexpensive prognostic factor that can help guide breast cancer treatments. However, prospective studies are needed to confirm this finding since the number of patients with progressive lymph nodes was limited in this study.
A large population-based study that used modern chemotherapy regimens and a similar follow-up time period as the present study reported a 2-year BCSS rate of 90% in patients with locally advanced breast cancers [18]. Another study with less modern treatment methods but a longer follow-up period surprisingly found no difference between retrospectively assessed breast cancer subgroups and patient survival [19]. Monneur et al. used a simplified breast cancer subtype classification (hormone-receptor-positive, HER2-positive or TNBC) in locally advanced breast cancers treated with NACT and reported a 5-year overall survival rate of 88%, with patients with TNBC having the worst prognosis [20]. We also recently reported long-term outcomes from a large prospective cohort from our institute in which we observed significant differences in the 10-year BCSS rates of different cancer subtypes, ranging from 97.6% for luminal A-like cancers to 80.6% for luminal B-like (HER2-positive) cancers (unpublished data). This is a striking difference compared to the very poor prognoses of the patient population used in this study. Although all the patients in the present study were immediately treated with a curative intention and were judged to be in relatively good health to receive NACT, every seventh patient with TNBC in our cohort died of breast cancer during the 2-year follow-up period. In addition, while the patients with luminal A-like breast cancer in the present cohort had large primary tumours, often with notable axillary involvement, and none of them achieved pCR, none of them died of breast cancer during our 2-year follow-up period either. Moreover, only 10.7% of our patients achieved pCR, which is markedly lower than is usually reported in the literature and indicates the local aggressiveness of the tumours in our cohort [16,21]. None of our patients received endocrine neoadjuvant treatment, which in theory could have improved the response rates of ER-positive patients, at least after progression and when combined with CDK4/6 inhibitor.
Our cohort included only a few patients with early lymph node progressions, which, along with the retrospective nature of the study and its short follow-up time, are clear limitations. Since our cohort consisted of large and locally advanced tumours, the results can not necessarily be generalised to more local breast cancers. However, patients in our cohort were uniformly diagnosed with very high-risk breast cancers, which partly compensates for the short follow-up length. Clinical examinations and high-quality MRI scans were performed after every second NACT cycle, and the MRI scans were evaluated by a breast radiologist. Furthermore, our end-point was BCSS, not overall survival, and the patients all received modern surgical, medical and radiotherapy treatments.
Overall, our results lead us to hypothesise that early radiological progression in axillary lymph nodes during NACT may predict poor outcomes for HER2-negative patients, although confirmatory studies with larger number of patients and events are obviously required. Early progression in all target lesions was also associated with poor prognoses across the whole patient cohort and the current results are suggestive for treatment change immediately after progression. The results also suggest the importance of frequent MRI follow-up during NACT. Although short-term prognoses varied by subtype, among this cohort with very large and locally advanced breast cancers, the prognoses were overall quite poor.
| N (%) | |
|---|---|
| Age at diagnosis | |
| Mean (min–max) | 55.2 (23–80) |
| Menopause status at diagnosis | |
| Pre-menopausal | 63 (43.4) |
| Peri-menopausal | 6 (4.1) |
| Post-menopausal | 74 (51.0) |
| Missing | 2 (1.4) |
| Prior breast cancer | |
| Yes | 5 (3.4) |
| No | 140 (96.6) |
| Bilateral breast cancer | |
| Yes | 8 (5.5) |
| No | 137 (94.5) |
| Status at most recent monitoring date | |
| Alive, no breast cancer | 119 (82.1) |
| Alive with breast cancer | 8 (5.5) |
| Died of breast cancer | 16 (11.0) |
| Died of other causes | 2 (1.4) |
| Neoadjuvant chemotherapy | |
| Docetaxel + doxorubicin/epirubicin | 82 (56.6) |
| Docetaxel | 7 (4.8) |
| Docetaxel + trastuzumab | 13 (9.0) |
| Docetaxel + trastuzumab + pertuzumab | 19 (13.1) |
| Other | 23 (15.9) |
| Missing | 1 (0.7) |
| Neoadjuvant trastuzumab | |
| Yes | 40 (27.6) |
| No | 105 (72.4) |
| Number of NACT cycles | |
| 2–5 | 10 (6.9) |
| 6 | 31 (21.4) |
| 7 | 17 (11.7) |
| 8 | 85 (58.6) |
| 10–12 | 2 (1.4) |
| Surgery performed | |
| Mastectomy + axillary lymph node dissection | 139 (95.9) |
| Other | 6 (4.1) |
| Adjuvant chemotherapy | |
| None | 132 (91.0) |
| CEF | 3 (2.1) |
| Capecitabine | 9 (6.2) |
| Other | 1 (0.7) |
| Adjuvant trastuzumab | |
| Yes | 41 (28.3) |
| No | 104 (71.7) |
| Adjuvant radiotherapy | |
| Yes | 142 (97.9) |
| No | 3 (2.1) |
| Adjuvant endocrine therapy | |
| None | 44 (30.3) |
| Tamoxifen | 31 (21.4) |
| Aromatase inhibitor | 52 (35.9) |
| LHRH analogue + TAM | 8 (5.5) |
| LHRH analogue + AI | 5 (3.4) |
| TAM + AI/AI + TAM | 4 (2.8) |
| Other | 1 (0.7) |
AI: aromatase inhibitor; CEF: cyclophosphamide, epirubicin and 5-fluorouracil; LHRH: luteinising hormone-releasing hormone agonist; NACT: neoadjuvant chemotherapy; TAM: tamoxifen.
| N (%) | |
|---|---|
| Lesion diameter in the breast (MRI) | |
| Mean (min–max), in mm | 65.3 (23–140) |
| Missing | 2 (1.4) |
| T class (pre-treatment MRI) | |
| T1 | 0 (0.0) |
| T2 | 31 (21.4) |
| T3 | 83 (57.2) |
| T4 | 30 (20.7) |
| Missing | 1 (0.7) |
| Inflammatory | |
| Yes | 21 (14.5) |
| No | 124 (85.5) |
| Axillary status | |
| Cytologically confirmed metastasis | 75 (51.7) |
| No confirmed metastases | 70 (48.3) |
| Histopathology | |
| Ductal | 110 (75.9) |
| Lobular | 27 (18.6) |
| Other | 8 (5.5) |
| Subtype | |
| Luminal A-like | 17 (11.7) |
| Luminal B-like (HER2-positive) | 20 (13.8) |
| Luminal B-like (HER2-negative) | 71 (49.0) |
| HER2-positive (non-luminal) | 20 (13.8) |
| Triple-negative | 17 (11.7) |
| Histopathological grade | |
| Grade 1 | 4 (2.8) |
| Grade 2 | 48 (33.1) |
| Grade 3 | 86 (59.3) |
| Missing | 7 (4.8) |
| Oestrogen receptor expression | |
| Negative (0%) | 37 (25.5) |
| Weak (1–9%) | 11 (7.6) |
| Moderate (10–59%) | 4 (2.8) |
| High (>59%) | 93 (64.1) |
| Progesterone receptor expression | |
| Negative (0%) | 55 (37.9) |
| Weak (1–9%) | 18 (12.4) |
| Moderate (10–59%) | 8 (5.5) |
| High (>59%) | 64 (44.1) |
| Ki-67 expression | |
| Negative (<5%) | 4 (2.8) |
| Weak (5–14%) | 18 (12.4) |
| Moderate (15–30%) | 32 (22.1) |
| High (>30%) | 90 (62.1) |
| Missing | 1 (0.7) |
| HER2 status | |
| Positive | 41 (28.3) |
| Negative | 104 (71.7) |
| N (%) | |
|---|---|
| Invasive cancer present in breast and/or axillary lymph nodes | |
| Yes | 123 (84.8) |
| Ductal | 83 (67.5) |
| Lobular | 28 (22.8) |
| Other | 8 (6.5) |
| Cancer only in axillary lymph nodes | 4 (3.2) |
| Only carcinoma in situ | 7 (4.8) |
| Benign changes only | 15 (10.3) |
| Malignant tumour diameter (mm) | 142 (97.9) |
| Mean (min–max) | 37.7 (0–100) |
| Missing | 3 (2.1) |
| ypT class | |
| ypT0 | 17 (11.7) |
| ypTis | 8 (5.5) |
| ypT1 | 47 (32.4) |
| ypT2 | 47 (32.4) |
| ypT3 | 25 (17.2) |
| ypT4 | 1 (0.7) |
| ppN class | |
| ypN0 | 58 (40.0) |
| ypN1 | 46 (31.7) |
| ypN2 | 27 (18.6) |
| ypN3 | 9 (6.2) |
| Missing | 5 (3.4) |
| Lymph node ratio (malignant/evaluated, %) | |
| Mean (min–max) | 17.6 (0–100) |
| Median | 17.6 |
| Missing | 5 (3.4) |
| Treatment response | |
| pCR in breasts and axillary lymph nodes | 15 (10.3) |
| Residual cancer in breasts or axillary lymph nodes | 130 (89.7) |
| rCR (%) | PR (%) | SD (%) | PD (%) | Missing (%) | |
|---|---|---|---|---|---|
| Luminal A-like | 0 | 11 (64.7) | 6 (35.5) | 0 | 0 |
| Luminal B-like (HER2+) | 3 (15.0) | 8 (40.0) | 8 (40.0) | 0 | 1 (5.0) |
| Luminal B-like (HER2−) | 3 (4.2) | 23 (32.4) | 32 (45.1) | 1 (1.4) | 12 (16.9) |
| HER2+ (non-luminal) | 3 (15.0) | 10 (50.0) | 4 (20.0) | 0 | 3 (15.0) |
| Triple-negative | 8 (47.1) | 7 (41.2) | 2 (11.8) | 0 |
rCR: radiological complete response (yT0N0); PR: partial response; SD: stable disease; PD: progressive disease. All results are based on magnetic resonance imaging scans.
Disclosure statement
There are no potential conflicts of interest.
References
- Gnant M, Harbeck N, Thomssen C. St. Gallen/Vienna 2017: a brief summary of the consensus discussion about escalation and de-escalation of primary breast cancer treatment. Breast Care (Basel). 2017;12(2):102–107. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Aittomäki K, Auvinen P, Heikkilä P, et al. Rintasyövän valtakunnallinen diagnostiikka – ja hoitosuositus. Finnish Breast Cancer Group; 2019. [Google Scholar]
- Roininen N, Haapasaari KM, Karihtala P. The role of redox-regulating enzymes in inoperable breast cancers treated with neoadjuvant chemotherapy. Oxid Med Cell Longev. 2017;2017:1–9. [Crossref], [Web of Science ®], [Google Scholar]
- Sobin LH, Gospodarowicz MK, Wittekind C. UICC TNM classification of malignant tumours, 7th ed. New York: Wiley-Blackwell; 2011. [Google Scholar]
- Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–172. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Fujihara M, Kin T, Yoshimura Y, et al. Prognostic factors after neoadjuvant chemotherapy in breast cancer: surgery type as a new prognostic factor. Annonc. 2016;27 (suppl.6):304. [Google Scholar]
- Marinovich ML, Sardanelli F, Ciatto S, et al. Early prediction of pathologic response to neoadjuvant therapy in breast cancer: systematic review of the accuracy of MRI. Breast. 2012;21(5):669–677. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Karihtala P, Mantyniemi A, Kang SW, et al. Peroxiredoxins in breast carcinoma. Clin Cancer Res. 2003;9(9):3418–3424. [PubMed], [Web of Science ®], [Google Scholar]
- Isola J, Tanner M, Forsyth A, et al. Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization. Clin Cancer Res. 2004;10(14):4793–4798. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Senkus E, Kyriakides S, Ohno S, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26 (suppl. 5):8. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1. Eur J Cancer. 2009;45(2):228–247. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Taourel P, Pages E, Millet I, et al. Magnetic resonance imaging in breast cancer management in the context of neo-adjuvant chemotherapy. Crit Rev Oncol Hematol. 2018;132:51–65. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Hylton NM, Blume JD, Bernreuter WK, et al. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy – results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012;263(3):663–672. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Wu LM, Hu JN, Gu HY, et al. Can diffusion-weighted MR imaging and contrast-enhanced MR imaging precisely evaluate and predict pathological response to neoadjuvant chemotherapy in patients with breast cancer? Breast Cancer Res Treat. 2012;135(1):17–28. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Morgan C, Stringfellow TD, Rolph R, et al. Neoadjuvant chemotherapy in patients with breast cancer: does response in the breast predict axillary node response? Eur J Surg Oncol. 2019; 46:522–526. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Gentile LF, Plitas G, Zabor EC, et al. Tumour biology predicts pathologic complete response to neoadjuvant chemotherapy in patients presenting with locally advanced breast cancer. Ann Surg Oncol. 2017;24(13):3896–3902. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Cerbelli B, Botticelli A, Pisano A, et al. Breast cancer subtypes affect the nodal response after neoadjuvant chemotherapy in locally advanced breast cancer: are we ready to endorse axillary conservation?. Breast J. 2019;25(2):273–277. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Dawood S, Ueno NT, Valero V, et al. Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early: a large population-based study. Cancer. 2011;117(9):1819–1826. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Stamatovic L, Susnjar S, Gavrilovic D, et al. The influence of breast cancer subtypes on the response to anthracycline neoadjuvant chemotherapy in locally advanced breast cancer patients. J Buon. 2018;23(5):1273–1280. [PubMed], [Web of Science ®], [Google Scholar]
- Monneur A, Goncalves A, Gilabert M, et al. Similar response profile to neoadjuvant chemotherapy, but different survival, in inflammatory versus locally advanced breast cancers. Oncotarget. 2017;8(39):66019–66032. [Crossref], [PubMed], [Google Scholar]
- Boughey JC, McCall LM, Ballman KV, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg. 2014;260(4):608–616. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]