Meagan Brennan

Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy

PURPOSE There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We review the evidence on surgical margins in BCT for early-stage invasive breast cancer. METHODS Meta-analysis of studies reporting local recurrence (LR) relative to quantified final microscopic margin status and the threshold distance for negative margins. The proportion of LR was modelled using random effects logistic meta-regression. RESULTS Based on 21 studies (LR in 1,026 of 14,571 subjects) the odds of LR were associated with margin status [model 1: odds ratio (OR) = 2.02 for positive/close versus negative; model 2: OR = 1.80 for close versus negative, 2.42 for positive versus negative (P<0.001 both models)] but not with margin distance [1mm versus 2mm versus 5mm (P > 0.10 both models)], adjusting for median follow-up time. However, there was weak evidence in both models that the odds of LR decreased as the threshold distance for declaring negative margins increased. This bordered significance in model 2 [OR for 1mm, 2mm, 5mm: 1.0, 0.75, 0.51 (P = 0.097 for trend)], and was not significant in model 1 [OR for 1mm, 2mm, 5mm: 1.0, 0.85, 0.58 (P = 0.11 for trend)] but was evident when one study (of women ≤ 40 years) was excluded from this model [OR for 1mm, 2mm, 5mm: 1.0, 0.72, 0.52 (P = 0.058 for trend)]: this trend was rendered insignificant by adjustment for the proportion of subjects receiving a radiation boost or the proportion of subjects receiving endocrine therapy. CONCLUSIONS Margin status has a prognostic effect in all women treated for invasive breast cancer; increasing the threshold distance for declaring negative margins is weakly associated with reduced odds of LR, however adjustment for covariates (adjuvant therapy) removes the significance of this effect. Adoption of wider margins, relative to narrower widths, for declaring negative margins is unlikely to a have substantial additional benefit for long-term local control in BCT.

Magnetic Resonance Imaging Screening of the Contralateral Breast in Women With Newly Diagnosed Breast Cancer: Systematic Review and Meta-Analysis of Incremental Cancer Detection and Impact on Surgical Management

PURPOSE Preoperative magnetic resonance imaging (MRI) is increasingly used for staging women with breast cancer, including screening for occult contralateral cancer. This article is a review and meta-analysis of studies reporting contralateral MRI in women with newly diagnosed invasive breast cancer. METHODS We systematically reviewed the evidence on contralateral MRI, calculating pooled estimates for positive predictive value (PPV), true-positive:false-positive ratio (TP:FP), and incremental cancer detection rate (ICDR) over conventional imaging. Random effects logistic regression examined whether estimates were associated with study quality or clinical variables. RESULTS Twenty-two studies reported contralateral malignancies detected only by MRI in 131 of 3,253 women. Summary estimates were as follows: MRI-detected suspicious findings (TP plus FP), 9.3% (95% CI, 5.8% to 14.7%); ICDR, 4.1% (95% CI, 2.7% to 6.0%), PPV, 47.9% (95% CI, 31.8% to 64.6%); TP:FP ratio, 0.92 (95% CI, 0.47 to 1.82). PPV was associated with the number of test positives and baseline imaging. Few studies included consecutive women, and few ascertained outcomes in all subjects. Where reported, 35.1% of MRI-detected cancers were ductal carcinoma in situ (mean size = 6.9 mm), 64.9% were invasive cancers (mean size = 9.3 mm), and the majority were stage pTis or pT1 and node negative. Effect on treatment was inconsistently reported, but many women underwent contralateral mastectomy. CONCLUSION MRI detects contralateral lesions in a substantial proportion of women, but does not reliably distinguish benign from malignant findings. Relatively high ICDR may be due to selection bias and/or overdetection. Women must be informed of the uncertain benefit and potential harm, including additional investigations and surgery.

Ductal Carcinoma in Situ at Core-Needle Biopsy: Meta-Analysis of Underestimation and Predictors of Invasive Breast Cancer

PURPOSE To perform a meta-analysis to report pooled estimates for underestimation of invasive breast cancer (where core-needle biopsy [CNB] shows ductal carcinoma in situ [DCIS] and excision histologic examination shows invasive breast cancer) and to identify preoperative variables that predict invasive breast cancer. MATERIALS AND METHODS Studies were identified by searching MEDLINE and were included if they provided data on DCIS underestimates (overall and according to preoperative variables). Study-specific and pooled percentages for DCIS underestimates were calculated. By using meta-regression (random effects logistic modeling) the association between each study-level preoperative variable and understaged invasive breast cancer was investigated. RESULTS Fifty-two studies that included 7350 cases of DCIS with findings at excision histologic examination as the reference standard met the eligibility criteria and were included. There were 1736 underestimates (invasive breast cancer at excision); the random-effects pooled estimate was 25.9% (95% confidence interval: 22.5%, 29.5%). Preoperative variables that showed significant univariate association with higher underestimation included the use of a 14-gauge automated device (vs 11-gauge vacuum-assisted biopsy, P = .006), high-grade lesion at CNB (vs non-high grade lesion, P < .001), lesion size larger than 20 mm at imaging (vs lesions ≤ 20 mm, P < .001), Breast Imaging Reporting and Data System (BI-RADS) score of 4 or 5 (vs BI-RADS score of 3, P for trend = .005), mammographic mass (vs calcification only, P < .001), and palpability (P < .001). CONCLUSION About one in four DCIS diagnoses at CNB represent understaged invasive breast cancer. Preoperative variables significantly associated with understaging include biopsy device and guidance method, size, grade, mammographic features, and palpability.

Early prediction of pathologic response to neoadjuvant therapy in breast cancer: Systematic review of the accuracy of MRI

Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRIs accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted.

Survivorship care plans in cancer: a systematic review of care plan outcomes

Background:Eight years after the Institute of Medicine recommended survivorship care plans (SCPs) for all cancer survivors, this study systematically reviewed the evidence for their use.Methods:Studies evaluating outcomes after implementation of SCPs for cancer survivors were identified by searching databases (MEDLINE, EMBASE and Cochrane). Data were extracted and summarised.Results:Ten prospective studies (2286 survivors) met inclusion criteria (5 randomised controlled trials (RCTs)). Study populations included survivors of breast, gynaecological, colorectal and childhood cancer. Several models of SCP were evaluated (paper based/on-line, oncologist/nurse/primary-care physician-delivered and different templates). No significant effect of SCPs was found on survivor distress, satisfaction with care, cancer-care coordination or oncological outcomes in RCTs. Breast cancer survivors with SCPs were better able to correctly identify the clinician responsible for their follow-up care. One study suggested a positive impact on reducing unmet needs. Levels of survivor satisfaction with, and self-reported understanding of, their SCP were very high. Feasibility was raised by health professionals as a significant barrier, as SCPs took 1–4 h of their time to develop.Conclusions:Emerging evidence shows very few measurable benefits of SCPs. Survivors reported high levels of satisfaction with SCPs. Resource issues were identified as a significant barrier to implementation.

Evaluation of the evidence on staging imaging for detection of asymptomatic distant metastases in newly diagnosed breast cancer

While guidelines recommend against routine use of staging imaging to detect asymptomatic distant metastases (DM) in newly diagnosed breast cancer (BC), modern imaging technologies may have improved detection capability and may have a role in some cases. We performed a systematic review of studies (1995-2011) evaluating the prevalence of DM and the accuracy of staging imaging for detection of asymptomatic DM. Twenty-two studies reporting on 14,824 BC subjects (median age 53 years) undergoing staging imaging were eligible. Median prevalence of DM was 7.0% (range 1.2-48.8%); prevalence increased with increasing BC stage. Conventional imaging studies had lower DM prevalence than studies of PET(PET/CT). Imaging median sensitivity/specificity respectively were: combined conventional imaging 78.0%/91.4%; bone scintigraphy 98.0%/93.5%; chest X-ray 100%/97.9%; liver ultrasound 100%/96.7%; CT chest/abdomen 100%/93.1%; FDG-PET 100.0%/96.5%; FDG-PET/CT 100%/98.1%. Low prevalence of DM was seen in Stage I-II BC with much higher prevalence in more advanced disease. Accuracy of PET modalities was very high however the high proportion of detected asymptomatic DM partly reflects selection bias.

Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy.

Background:Magnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI’s agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of agreement.Methods:A systematic literature search was undertaken. Mean differences (MDs) in tumour size between MRI or comparator tests and pathology were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated from a pooled variance by assuming equal variance of the differences across studies.Results:Data were extracted from 19 studies (958 patients). The pooled MD between MRI and pathology from six studies was 0.1 cm (95% LOA: −4.2 to 4.4 cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm) was observed, with comparable LOA (two studies). Overestimation was lower for MRI (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: −0.3 cm). The LOA for mammography and clinical examination were wider than that for MRI. Percentage agreement between MRI and pathology was greater than that of comparator tests (six studies). The range of Pearson’s/Spearman’s correlations was wide (0.21–0.92; 16 studies). Inconsistencies between MDs, percentage agreement and correlations were common.Conclusion:Magnetic resonance imaging appears to slightly overestimate pathologic size, but measurement errors may be large enough to be clinically significant. Comparable performance by US was observed, but agreement with pathology was poorer for mammography and clinical examination. Percentage agreement can provide supplementary information to MDs and LOA, but Pearson’s/Spearman’s correlation does not provide evidence of agreement and should be avoided. Further comparisons of MRI and other tests using the recommended methods are warranted.

Survivorship care after breast cancer: follow-up practices of Australian health professionals and attitudes to a survivorship care plan.

Objective:  The increasing number of breast cancer survivors and the complexity of follow‐up care make the provision of high‐quality survivorship care a challenge. This study explored the follow‐up practices of health professionals and their attitudes to alternative models such as shared care and the use of a survivorship care plan.

Increasing breast reconstruction rates by offering more women a choice

Breast reconstruction (BR) following mastectomy for breast cancer is safe and has high rates of patient satisfaction, yet only around 12% of Australian women undergo BR. This study presents BR rates and outcomes from a specialist practice that discusses reconstruction options with all women medically suitable for BR.

Patterns and outcomes of breast reconstruction in older women – A systematic review of the literature

PURPOSE Older age is associated with lower rates of breast reconstruction (BR) for women requiring mastectomy. The purpose was to assess the available evidence on uptake, outcome and quality of life (QoL) after BR in older women. METHODS A systematic literature review was performed via Medline, Embase and Cochrane databases using the search terms breast reconstruction, breast cancer, and mastectomy. Eligible studies reported rates of BR, rates of different reconstructive techniques, complication rates, and/or patient reported outcome measures (PROMs) of BR in women aged 60 years or older undergoing mastectomy for ductal carcinoma in situ or invasive carcinoma. RESULTS A total of 42 eligible studies were included, with 32 of these reporting BR rates, 10 reporting rates of different reconstructive techniques, 10 reporting rates of complications, and four reporting PROMs. The studies reported 24,746 cases of BR in 407,570 mastectomy patients aged 60 years or older from 1987 to 2012. Implant based BR was more common than autologous techniques. Mostly, complication rates were not higher in older women, and QoL outcomes were similar to younger women. CONCLUSIONS This review confirms that BR rates are lower in older women despite recent studies demonstrating its efficacy. The perception among some surgeons and women requiring mastectomy that the potential risks of BR in older women outweigh the benefits needs to be revisited. Education of consumers and surgeons along with public advocacy for offering BR to all clinically eligible women are the most promising means of changing practice.