Survival is associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.

BACKGROUND: Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We explored whether response evaluation by magnetic resonance imaging (MRI) is associated with recurrence-free survival after NAC in ER-positive/HER2-negative breast cancer. METHODS: MRI examinations were performed in 272 women with ER-positive/HER2-negative breast cancer before, during and after NAC. MRI interpretation included lesion morphology at baseline, changes in morphology and size, and contrast uptake kinetics. These MRI features, clinical characteristics and final pathology were correlated with recurrence-free survival. RESULTS: The median follow up time was 41 months. There were 35 women with events, including 19 breast-cancer-related deaths. On multivariable analysis, age younger than 50 years (hazard ratio (HR) = 2.55, 95 % confidence interval (CI) 1.3, 5.02, p = 0.007), radiological complete response after NAC (HR = 14.11, CI 1.81, 1818; p = 0.006) and smaller diameters of washout/plateau enhancement at MRI after NAC (HR = 1.02, CI 1.00, 1.04, p = 0.036) were independently associated with best recurrence-free survival. Pathological response was not significant; HR = 2.12, CI 0.86, 4.64, p = 0.096. CONCLUSIONS: MRI after NAC in ER-positive/HER2-negative tumors may be predictive of recurrence-free survival. A radiological complete response at MRI after NAC is associated with an excellent prognosis.

Sequential (18)F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy.

PURPOSE: To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. METHODS: In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. RESULTS: A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. CONCLUSION: In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR.

Combined use of ¹8F-FDG PET/CT and MRI for response monitoring of breast cancer during neoadjuvant chemotherapy.

PURPOSE: To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype. METHODS: We performed (18)F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in (18)F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses. RESULTS: Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p = 0.033), breast cancer subtype (p < 0.001), relative change in SUVmax on PET/CT (p < 0.001) and relative change in largest tumour diameter on MRI (p < 0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95% CI 0.68-0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95% CI 0.70-0.89). The AUC increased to 0.90 (95% CI 0.83-0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p = 0.012). CONCLUSION: PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype.

Radioactive seed localization of breast lesions: an adequate localization method without seed migration.

Preoperative localization is important to optimize the surgical treatment of breast lesions, especially in nonpalpable lesions. Radioactive seed localization (RSL) using iodine-125 is a relatively new approach. To provide accurate guidance to surgery, it is important that the seeds do not migrate after placement. The aim of this study was to assess short-term and long-term seed migration after RSL of breast lesions. In 45 patients, 48 RSL procedures were performed under ultrasound or stereotactic guidance. In the first 12 patients, the lesion was localized with two markers: an iodine-125 seed and a reference marker. In 33 patients, 36 RSL procedures were performed using a single iodine-125 seed. All patients received control mammograms after seed placement and prior to surgery. In the patients with two markers, migration was defined as the difference in the largest distance between the markers observed in the mammograms. For single-marked lesions, migration was assessed by comparing distances between anatomical landmarks in the mammograms. RSL was successful in all patients. Seeds were in-situ for 59.5 days on average (3-136 days). The detection rate during surgery was 100%. Overall, an average seed migration of 0.9 mm (standard deviation 1.0 mm) was observed. Neither differences in lesion type, nor days in situ, type of surgery or radiologic localization method were found to have impact on seed migration. RSL is an accurate preoperative localization method for breast lesions with negligible seed migration, independent of time in-situ.

A practical approach to manage additional lesions at preoperative breast MRI in patients eligible for breast conserving therapy: results.

The aim of this prospective study was to evaluate the efficacy of directives, established to handle additional lesions at preoperative contrast-enhanced magnetic resonance imaging (MRI). Six-hundred-and-ninety consecutive patients with pathology-proven breast cancer planned for BCT based on clinical examination and conventional imaging underwent preoperative breast MRI. The incidence of additional lesions detected at MRI and impact on management were evaluated. Additional findings were pathology-proven or considered benign by follow-up. Findings for which no pathology proof was available prior to surgery, were defined as Unidentified Breast Objects (UBOs). Patients with multicentric or contralateral UBOs underwent BCT as planned with annual follow-up. Multifocal UBOs in the vicinity of the index cancer were excised with wider local margins. Preoperative MRI detected 141 additional lesions in 121 patients (17.5%). Of these lesions, 44.0% were proven malignant. Additional findings classified as UBOs were found in 81 patients (11.7%). None of the UBOs outside the primary tumour region resulted in malignant disease at follow-up after BCT (mean follow-up time: 57.1 months). However, most multifocal UBOs (in the vicinity of the primary) were malignant (77.5%). The strategy to pursue BCT with larger wide-local excisions for multifocal UBOs and to follow-up multicentric and contralateral UBOs with conventional imaging is effective to exclude malignancy at follow-up. After second-look targeted ultrasound has been performed, MRI-guided biopsy of BIRADS-3 multicentric and contralateral additional findings may have limited complementary clinical value.

Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes.

PURPOSE: To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. MATERIALS AND METHODS: In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and 18F-FDG-PET/CT were acquired before and during NAC. Baseline pathology was assessed from tumor biopsy. Tumors were stratified into HER2-positive, ER-positive/HER2-negative (ER-positive), and ER-negative/PR-negative/HER2-negative (triple-negative) subtypes, and treated according to subtype. Primary endpoint was pathological complete response (pCRmic) defined as no or only small numbers of scattered invasive tumor cells. We evaluated imaging scenarios using MRI only, PET/CT only, and combinations. RESULTS: pCRmic was found in 35/46 (76.1%) of HER2-positive, 11/87 (12.6%) of ER-positive, and 31/55 (56.4%) of triple-negative tumors. For HER2-positive tumors, MRI yielded the strongest predictor (AUC: 0.735; sensitivity 36.2%), outperforming PET/CT (AUC: 0.543; p = 0.04), and with comparable results to combined imaging (AUC: 0.708; p = 0.213). In ER-positive tumors, the combination of MRI and PET/CT was slightly superior (AUC: 0.818; sensitivity 55.8%) over MRI alone (AUC: 0.742; p = 0.117) and PET/CT alone (AUC: 0.791). However, even though relatively large numbers of ER-positive tumor patients were included, no significant differences were yet found. For triple-negative tumors, MRI (AUC: 0.855; sensitivity 45.4%), PET/CT (AUC: 0.844; p = 0.220) and combined imaging (AUC: 0.868; p = 0.213) yielded comparable results. CONCLUSIONS: For HER2-positive tumors, MRI shows significant advantage over PET/CT. For triple-negative tumors, comparable results were seen for MRI, PET/CT and combined imaging. For ER-positive tumors, combining MRI with PET/CT may result in optimal response monitoring, although not yet significantly.

Additional value of 18F-FDG PET/CT response evaluation in axillary nodes during neoadjuvant therapy for triple-negative and HER2-positive breast cancer.

BACKGROUND: 18F-FDG PET/CT can monitor metabolic activity in early breast cancer during neoadjuvant systemic therapy (NST), but it is unknown if the metabolic breast and axillary response differ. We evaluated the correlation between metabolic breast and axillary response at various time points during NST. Furthermore, we analysed if the combined metabolic response improves pathologic complete response (pCR) prediction compared to using the metabolic breast response alone. METHODS: 18F-FDG PET/CT was performed at baseline (PET1), 2-3 weeks (PET2), and 6-8 weeks (PET3) of NST in patients with triple-negative (TN) and HER2-positive node-positive breast cancer. SUVmax and ∆SUVmax were determined separately for breast and axilla. Spearman's correlation coefficients (r) between both localisations were calculated. The accuracy of pCR total (ypT0/is,ypN0) prediction using the metabolic response in breast, axilla or both was examined using logistic regression analysis. RESULTS: Hundred-five patients were included: 45 TN and 60 HER2-positive tumours. The metabolic response in breast and axilla correlated moderately in TN tumours (r = 0.57) using ∆SUVmax between PET1-PET3 and poorly in HER2-positive tumours (r = 0.49) using SUVmax at PET2. In TN tumours, metabolic breast response predicted pCR well without improvement after adding axillary response (c-index 0.82 versus 0.85, p = 0.63). In HER2-positive tumours, metabolic breast response predicted pCR poorly with improvement after adding axillary response (c-index 0.64 versus 0.72, p = 0.06). CONCLUSIONS: 18F-FDG PET/CT response during NST differs between breast and axilla. In TN tumours, pCR total prediction can be made independent of metabolic axillary response. In HER2-positive tumours, axillary response may improve pCR total prediction. These findings may help guide PET/CT-response-based changes during NST. TRIAL REGISTRATION: NTR NTR1797 . Registered 29 May 2009, retrospectively registered.

Avoiding preoperative breast MRI when conventional imaging is sufficient to stage patients eligible for breast conserving therapy.

AIM: To determine when preoperative breast MRI will not be more informative than available breast imaging and can be omitted in patients eligible for breast conserving therapy (BCT). METHODS: We performed an MRI in 685 consecutive patients with 692 invasive breast tumors and eligible for BCT based on conventional imaging and clinical examination. We explored associations between patient, tumor, and conventional imaging characteristics and similarity with MRI findings. Receiver operating characteristic (ROC) analysis was employed to compute the area under the curve (AUC). RESULTS: MRI and conventional breast imaging were similar in 585 of the 692 tumors (85%). At univariate analysis, age (p<0.001), negative preoperative lymph node status (p=0.011), comparable tumor diameter at mammography and at ultrasound (p=0.001), negative HER2 status (p=0.044), and absence of invasive lobular cancer (p=0.005) were significantly associated with this similarity. At multivariate analysis, these factors, except HER2 status, retained significant associations. The AUC was 0.68. CONCLUSIONS: It is feasible to identify a subgroup of patients prior to preoperative breast MRI, who will most likely show similar results on conventional imaging as on MRI. These findings enable formulation of a practical consensus guideline to determine in which patients a preoperative breast MRI can be omitted.

FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative, but not in HER2-positive breast cancer.

BACKGROUND: Response monitoring with MRI during neoadjuvant chemotherapy (NAC) in breast cancer is promising, but knowledge of breast cancer subtype is essential. The aim of the present study was to evaluate the relevance of breast cancer subtypes for monitoring of therapy response during NAC with 18F-FDG PET/CT. METHODS: Evaluation included 98 women with stages II and III breast cancer. PET/CTs were performed before and after six or eight weeks of NAC. FDG uptake was quantified using maximum standardized uptake values (SUVmax). Tumors were divided into three subtypes: HER2-positive, ER-positive/HER2-negative, and triple negative. Tumor response at surgery was assessed dichotomously (presence or absence of residual disease) and ordinally (breast response index, representing relative change in tumor stage). Multivariate regression and receiver operating characteristic (ROC) analyses were employed to determine associations with pathological response. RESULTS: A (near) complete pathological response was seen in 19 (76%) of 25 HER2-positive, 7 (16%) of 45 ER-positive/HER2-negative, and 20 (71%) of 28 triple negative tumors. Multivariate regression of pathological response indicated a significant interaction between change in FDG uptake and breast cancer subtype. The area under the ROC curve was 0.35 (0.12-0.64) for HER2-positive, 0.90 (0.76-1.00) for ER-positive/HER2-negative, and 0.96 (0.86-1.00) for triple negative tumors. We found no association between age, stage, histology, or baseline SUVmax and pathological response. CONCLUSION: Response monitoring with PET/CT during NAC in breast cancer seems feasible, but is dependent on the breast cancer subtype. PET/CT may predict response in ER-positive/HER2-negative and triple negative tumors, but seems less accurate in HER2-positive tumors.

Pre-treatment imaging and pathology characteristics of invasive breast cancers of limited extent: potential relevance for MRI-guided localized therapy.

BACKGROUND AND PURPOSE: Identifying breast cancers of limited extent (BCLE) is becoming increasingly important, especially for (image guided) minimally invasive therapy and partial breast irradiation. The purpose of this study is to establish characteristics at functional imaging and pathology associated with invasive BCLE. MATERIALS AND METHODS: Seventy-five patients (77 breasts) with invasive breast cancer were prospectively included. Excision specimens were processed using complete embedding. Microscopic findings were reconstructed and correlated with contrast-enhanced MRI. Tumors were stratified by absence or presence of occult disease ≥10 mm from the MRI-visible lesion: BCLE and non-BCLE, respectively. Imaging and pathology characteristics were evaluated for their ability to discriminate between BCLE and non-BCLE. Multivariate binary logistic regression was employed to create a prediction model for BCLE. RESULTS: At univariate analysis, imaging as well as pathology characteristics were indicative for BCLE (39/77=51%). At multivariate analysis, a mass on mammography, the absence of tumor washout, positive ER and low quantity of DCIS in the index tumor retained significance (area under ROC curve=0.87). CONCLUSIONS: Pre-treatment assessment of mammography findings, MRI washout kinetics, ER status and quantity of DCIS in the index tumor has the potential to accurately identify BCLE.