P.H.M. Peeters

Preoperative MRI and surgical management in patients with nonpalpable breast cancer: The MONET - Randomised controlled trial

BACKGROUNDnWe evaluated whether performing contrast-enhanced breast MRI in addition to mammography and/or ultrasound in patients with nonpalpable suspicious breast lesions improves breast cancer management.nnnMETHODSnThe MONET - study (MR mammography of nonpalpable breast tumours) is a randomised controlled trial in patients with a nonpalpable BIRADS 3-5 lesion. Patients were randomly assigned to receive routine medical care, including mammography, ultrasound and lesion sampling by large core needle biopsy or additional MRI preceding biopsy. Patients with cancer were referred for surgery. Primary end-point was the rate of additional surgical procedures (re-excisions and conversion to mastectomy) in patients with a nonpalpable breast cancer.nnnFINDINGSnFour hundred and eighteen patients were randomised, 207 patients were allocated to MRI, and 211 patients to the control group. In the MRI group 74 patients had 83 malignant lesions, compared to 75 patients with 80 malignant lesions in the control group. The primary breast conserving surgery (BCS) rate was similar in both groups; 68% in the MRI group versus 66% in the control group. The number of re-excisions performed because of positive resection margins after primary BCS was increased in the MRI group; 18/53 (34%) patients in the MRI group versus 6/50 (12%) in the control group (p=0.008). The number of conversions to mastectomy did not differ significantly between groups. Overall, the rate of an additional surgical intervention (BCS and mastectomy combined) after initial breast conserving surgery was 24/53 (45%) in the MRI group versus 14/50 (28%) in the control group (p=0.069).nnnINTERPRETATIONnAddition of MRI to routine clinical care in patients with nonpalpable breast cancer was paradoxically associated with an increased re-excision rate. Breast MRI should not be used routinely for preoperative work-up of patients with nonpalpable breast cancer.

Diagnostic accuracy for different strategies of image-guided breast intervention in cases of nonpalpable breast lesions

To find out whether ultrasound-guided fine-needle aspiration (FNA) and ultrasound and stereotactic-guided large core needle biopsy (LCNB) are reliable alternatives to needle-localised open breast biopsy (NLBB) in daily practice, we performed a retrospective study and evaluated the validity of these methods. In all, 718 women with 749 nonpalpable breast lesions from three Dutch Hospitals were included, and the validity of the various methods for diagnosis was assessed. This was carried out according to a method described by Burbank and Parker for evaluating the quality of an image-guided breast intervention. We compared our results with the outcome of the COBRA study. Overall, all diagnostic strategies (NLBB, FNA, LCNB ultrasound and stereotactic guided) show comparable agreement rates. However, the miss rates differ: 2% for NLBB, 3% for COBRA (LCNB in study setting), 5% for FNA and 8–12% for LCNB in practice. Fine-needle aspiration was nonconclusive in 29%, and shows an overestimation for DCIS in 9%. The DCIS underestimate rate in NLBB was 8%. For the assessment of lesions consisting of microcalcifications only and to exclude malignancy in all other lesions, a 14-gauge needle should be used. Ultrasound-guided intervention can be performed in a large percentage of nonpalpable lesions. Lesions consisting only of microcalcifications on mammography need special attention.

Vacuum-assisted breast biopsy: a critical review

Vacuum-assisted biopsy is an image-guided technique introduced in 1995 that is thought to be superior to 14G automated-needle biopsy for the evaluation of non-palpable breast lesions. However, prospective randomised studies evaluating its accuracy are unavailable. We conducted a critical review of the currently available literature on the accuracy of vacuum-assisted biopsy and compared it with published data on the accuracy of 14G automated-needle biopsy. The diagnostic performance of vacuum-assisted biopsy was evaluated by reviewing all available English-language literature published in Medline between 1995 and November 2001. Four independent reviewers used standard forms to extract the data. Twenty-two published studies were included. High-risk and DCIS underestimate rates, as well as the miss-rate of cancer, were assessed. High-risk and DCIS underestimate rates for 11G vacuum biopsy were 16% (95% Confidence Interval (CI) 12-20%) and 11% (95% CI 9-12%), respectively, and both were lower than the rates reported for 14G automated-needle biopsy (40% (95% CI 26%;56%) and 15% (95% CI 8%;26%), respectively). Due to incomplete follow-up of the benign lesions, it was impossible to calculate the miss-rates and the sensitivity rate. The results of this review indicate that vacuum-assisted biopsy can decrease the high-risk and DCIS underestimate rates, but it is unclear whether it can also decrease the miss-rates of cancer.

Volumetric Breast Density from Full-Field Digital Mammograms and Its Association with Breast Cancer Risk Factors: A Comparison with a Threshold Method

Introduction: Breast density, a strong breast cancer risk factor, is usually measured on the projected breast area from film screen mammograms. This is far from ideal, as breast thickness and technical characteristics are not taken into account. We investigated whether volumetric density measurements on full-field digital mammography (FFDM) are more strongly related to breast cancer risk factors than measurements with a computer-assisted threshold method. Methods: Breast density was measured on FFDMs from 370 breast cancer screening participants, using a computer-assisted threshold method and a volumetric method. The distribution of breast cancer risk factors among quintiles of density was compared between both methods. We adjusted for age and body mass index (BMI) with linear regression analysis. Results: High percent density was strongly related to younger age, lower BMI, nulliparity, late age at first delivery and pre/perimenopausal status, to the same extent with both methods (all P < 0.05). Similarly strong relationships were seen for the absolute dense area but to a lesser extent for absolute dense volume. A larger dense volume was only significantly associated with late age at menopause, use of menopausal hormone therapy, and, in contrast to the other methods, high BMI. Conclusion: Both methods related equally well to known breast cancer risk factors. Impact: Despite its alleged higher precision, the volumetric method was not more strongly related to breast cancer risk factors. This is in agreement with other studies. The definitive relationship with breast cancer risk still needs to be investigated. Cancer Epidemiol Biomarkers Prev; 19(12); 3096–105. ©2010 AACR.

Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients: Identification rate and influence on axillary treatment

The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The Netherlands. Patients diagnosed with clinically node negative primary breast cancer between 1st January 2010 and 30th June 2013 who received NAC and SNB were selected from the Netherlands Cancer Registry. Data on patient and tumour characteristics, axillary staging and treatment were analysed. Two groups were defined: (1) patients with SNB before NAC (N=980) and (2) patients with SNB after NAC (N=203). Eighty-three percent of patients underwent SNB before NAC, with large regional variation (35-99%). The SN identification rate differed for SNBs conducted before and after NAC (98% versus 95%; p=0.032). A lower proportion of patients had a negative SNB when assessed before NAC compared to after (54% versus 67%; p=0.001). The proportion of patients receiving any axillary treatment was higher for those with SNB before NAC than after (45% versus 33%; p=0.006). In conclusion, variation exists in the timing of SNB in clinical practice in The Netherlands for clinically node negative breast cancer patients receiving NAC. The post-NAC SN procedure is, despite some lower SN identification rate, associated with a significantly less frequent axillary treatment and thus with less expected morbidity. The effect on recurrence rate is not yet clear. Patients in this registry will be followed prospectively for long-term outcome.

The Value of Ipsilateral Breast Tumor Recurrence as a Quality Indicator: Hospital Variation in the Netherlands.

PurposeAll Dutch hospitals are obliged to report their 5-year ipsilateral breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided that these rates should not exceed 5xa0%. This study determined the value of IBTR as an indicator to compare quality of care between hospitals.MethodsAll patients with breast cancer (pT1–3, any N, M0) who underwent surgery in 1 of 92 Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer Registry. Data of recurrence was retrieved from hospital records. Five-year IBTR rates for breast-conserving surgery (BCS) and mastectomy were calculated by using the Kaplan–Meier method. Hospital variation was presented in funnel plots. Multivariate analysis was used to assess hospital characteristics associated with IBTR rates.ResultsA total of 40,892 breast cancer patients were included. The overall 5-year IBTR rate was 2.85xa0% (95xa0% confidence interval 2.68–3.03) and was significantly lower for BCS than for mastectomy (2.38 vs. 3.45xa0%, pxa0<xa00.001). IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70xa0% between hospitals. When random variation is taken into account, only extremely high IBTR rates can be detected as deviant from the target value of 5xa0%. Adjusting for tumor and patient characteristics, analyses showed that a higher volume of mastectomies is associated with lower IBTR rates.ConclusionsOur population-based findings show that IBTR rates in the Netherlands are low and have improved over time. The 5-year IBTR rate as an indicator for quality of care of individual hospitals is of limited value.

3-T breast magnetic resonance imaging in patients with suspicious microcalcifications on mammography

ObjectiveTo investigate the diagnostic value of 3-Tesla (T) breast MRI in patients presenting with microcalcifications on mammography.MethodsBetween January 2006 and May 2009, 123 patients with mammographically detected BI-RADS 3–5 microcalcifications underwent 3-T breast MRI before undergoing breast biopsy. All MRIs of the histopathologically confirmed index lesions were reviewed by two breast radiologists. The detection rate of invasive carcinoma and ductal carcinoma in situ (DCIS) was evaluated, as well as the added diagnostic value of MRI over mammography and breast ultrasound.ResultsAt pathology, 40/123 (33xa0%) lesions proved malignant; 28 (70xa0%) DCIS and 12 (30xa0%) invasive carcinoma. Both observers detected all invasive malignancies at MRI, as well as 79xa0% (observer 1) and 86xa0% (observer 2) of in situ lesions. MRI in addition to conventional imaging led to a significant increase in area under the receiver operating characteristic (ROC) curve from 0.67 (95xa0% CI 0.56–0.79) to 0.79 (95xa0% CI 0.70–0.88, observer 1) and to 0.80 (95xa0% CI 0.71–0.89, observer 2), respectively.Conclusions3-T breast MRI was shown to add significant value to conventional imaging in patients presenting with suspicious microcalcifications on mammography.Key points• 3-T MRI is increasingly used for breast imaging in clinical practice.• On 3-T breast MRI up to 86xa0% of DCIS lesions are detected.• 3-T MRI increases the diagnostic value in patients with mammographically detected microcalcifications.

Stereotactic large core needle biopsy for all nonpalpable breast lesions

AbstractBackground Stereotactic large-core needle biopsy (SLCNB) is a minimally invasive method for histological diagnosis of nonpalpable breast disease. We studied differences in cancer prevalence between a group of women referred through the national screening program and a non-screening group, and assessed whether the validity of SLCNB differed between these groups.nMethods A group of non-selective, consecutive patients presenting with a nonpalpable mammographic lesion, who participated in a recently conducted multicenter study regarding the accuracy of SLCNB in The Netherlands, were the basis for this study. Prevalence of carcinoma, predictive value of a benign diagnosis, sensitivity, and specificity rate of SLCNB were compared between the two groups.nResults Of the 1029 lesions in 972 patients included, 858 were evaluable. In 850/858 lesions (99.1%) the reason for referral was clear. The prevalence of cancer in the screening group (nu2009=u2009511 lesions) was 64.0% (95%CIu200959.8–68.2), versus 49.6% in the non-screening group (nu2009=u2009339) (95%CIu200944.2–54.9). Respective predictive values of a benign diagnosis on SLCNB were 97.0 versus 94.8% (non-significant). The sensitivity rates of SLCNB were 98.5% (screening; 95%CIu200996.5–99.5) versus 95.2% (non-screening; 95%CIu200990.8–97.9). Specificity rates were 97.8 (95%CIu200994.5–99.4) and 99.4% (95%CIu200996.8–100), respectively.nConclusion Despite a significant difference in the prevalence of carcinoma, the accuracy of SLCNB did not show a statistically significant difference between both patient groups. Therefore, SLCNB appears accurate in diagnosing nonpalpable breast lesions both in screening and non-screening patient groups.

Surgical Outcome of Patients with Core-Biopsy-Proven Nonpalpable Breast Carcinoma: A Large Cohort Follow-Up Study

BackgroundBreast-conserving surgery (BCS) is the preferred treatment for nonpalpable breast carcinoma. The outcome, however, may be disappointing. In this study surgical outcome in a large cohort of patients diagnosed with nonpalpable breast carcinoma is evaluated.MethodsIn 833 patients with 841 nonpalpable breast carcinomas the number of re-excisions and type of surgical procedures was calculated and summed per patient. Subsequently, the number of conversions to mastectomy and the number of days until complete tumor removal were analyzed. In a subgroup analysis the patients with an in situ carcinoma were compared with the patients with an invasive carcinoma.ResultsThe initial surgery consisted of BCS for 589 tumors (70%) and of mastectomy for 242 tumors (29%). For ten tumors (1%) the initial surgery was unknown. After BCS, 158/589 tumors (27%) required a re-excision: 116/337 (34%) for the in situ carcinomas and 63/504 (13%) for the invasive carcinomas (pxa0=xa00.0001). The number of conversions from BCS to mastectomy was 106/589 (18%): 66/241 (28%) in patients diagnosed with an in situ carcinoma versus 40/348 (11%) in patients with an invasive carcinoma (pxa0=xa00.0001). The median number of days until complete tumor removal was 28, being 38xa0days for the in situ carcinomas and 25xa0days for the invasive carcinomas (pxa0=xa00.0001).ConclusionsThere is room for improvement in the surgical treatment of nonpalpable breast carcinoma, especially the relatively favorable in situ carcinoma, as it requires significantly more excisions, mastectomies, conversions to mastectomy, and days for complete removal.

Abstract P1-10-09: Are patients with breast cancer undergoing adjuvant treatment able to follow an exercise program with a moderate to high intensity?

PURPOSE: We recently showed in a randomized trial, the Physical Activity during Cancer Treatment (PACT) study, that an 18-week exercise program reduced complaints of fatigue and improved physical fitness in newly diagnosed breast cancer patients undergoing adjuvant treatment. The beneficial effects were probably underestimated due to high levels of physical activity in the control group that received usual care only. Another possibility for dilution of the effect might be limited participation of the intervention group in the supervised exercise program or low compliance, i.e., an adjustment of the prescribed exercise protocol. We set out to study participation and compliance and to find determinants of reduced compliance. METHODS: 102 patients in the PACT study were randomized into the intervention group that received a supervised exercise program 2 times a week for 18 weeks (36 sessions in total). Each session had a duration of 60 minutes and included a pre-specified period of aerobic interval exercises of specific intensities as well as muscle strength exercises. Sessions were supervised by physiotherapists, intensity was based on individual fitness characteristics and results were kept in a log. We computed attendance (percentage of total sessions attended) and compliance (adherence to the prescribed duration and intensity of the aerobic part and to the muscle strength part of each attended session). We computed for each woman the percentage of sessions the women complied with the protocol, and report median percentages for compliance with the aerobic exercises, duration and intensity, and with the muscle strength exercises separately. Determinants of low compliance that were included in linear regression models were: age, behavioral, physical and psychosocial factors. RESULTS: For 92 patients exercise logs were available. Patients were, on average, 50.2±7.8 years of age, all patients received chemotherapy and 70% received radiotherapy. Participation was high: patients participated in 83% (interquartile range 69-91%) of the sessions offered. Overall, also compliance was high: in 88% (63-97%) and 84% (65-94%) of all attended sessions patients were able to complete the aerobic (duration) and muscle strength program, respectively, as prescribed in the protocol. Compliance to the high-intensity part of the aerobic program was lower: in 50% (22-82%) of the sessions the intensity of the aerobic exercises was adjusted. Especially patients who received radiotherapy in addition to chemotherapy and patients who were more physically fatigued at baseline had a lower compliance to the high-intensity part of the aerobic exercises (β=-5.3 (confidence interval -9.4;-1.2) and β=-0.6 (-1.0;-0.1), respectively). CONLUSIONS: Participation in and compliance to an 18-week aerobic and muscle strength exercise program was high. Thus, patients are well capable to exercise during adjuvant treatment for breast cancer. This study shows that preferably high intensity aerobic exercises were adjusted in a significant number of participants rather than the duration or the strength exercises. This has to be taken into account when developing training programs, especially in those patients who receive both, radiotherapy and chemotherapy. Citation Format: May AM, Boer JH, Velthuis M, Steins Bisschop CN, Los M, Erdkamp F, ten Bokkel Huinink D, Bloemendal HJ, Rodenhuis C, de Roos MAJ, Verhaar M, van der Wall E, Peeters PHM. Are patients with breast cancer undergoing adjuvant treatment able to follow an exercise program with a moderate to high intensity?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-09.