S Heys

Monitoring primary breast cancer throughout chemotherapy using FDG-PET.

We have compared 2-deoxy-2-[18F]-fluoro-d-glucose positron emission tomography (FDG-PET) images of large or locally advanced breast cancers (LABC) acquired during Anthracycline-based chemotherapy. The purpose was to determine whether there is an optimal method for defining tumour volume and an optimal imaging time for predicting pathologic chemotherapy response. Method: PET data were acquired before the first and second cycles, at the midpoint and at the endpoint of neoadjuvant chemotherapy. FDG uptake was quantified using the mean and maximum standardized uptake values (SUV) and the coefficient of variation within a region of interest. Receiver-operator characteristic (ROC) analysis was used to determine the discrimination between tumours demonstrating a high pathological response (i.e. those with greater than 90% reduction in viable tumour cells) and low pathological response. Results: Only tumours with an initial tumour to background ratio (TBR) of greater than five showed a difference between response categories. In terms of response discrimination, there was no statistically significant advantage of any of the methods used for image quantification or any of the time points. The best discrimination was measured for mean SUV at the midpoint of therapy, which identified 77% of low responding tumours whilst correctly identifying 100% of high responding tumours and had an ROC area of 0.93. Conclusion: FDG-PET is efficacious for predicting the pathologic response of most primary breast tumours throughout the duration of a neoadjuvant chemotherapy regimen. However, this technique is ineffective for tumours with low image contrast on pre-therapy PET scans.

Psychological factors can predict the response to primary chemotherapy in patients with locally advanced breast cancer

This study evaluated the possible value of psychological variables in predicting clinical and pathological response to primary chemotherapy. 96 women with newly diagnosed large, or locally advanced, breast cancer (T2 > 4 cm, T3, T4, N2 and M0) participated in a prospective, randomised trial to evaluate the effects of relaxation training with guided imagery and L-arginine on response to primary chemotherapy. Before the first of six cycles of primary chemotherapy, women were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Eysenck Personality Questionnaire (EPQ). The primary outcomes were clinical response (evaluated using standard International Union Against Cancer (UICC) criteria) and pathological response (graded by means of a previously published 5-point scale) following primary chemotherapy. Stepwise linear regressions were used to estimate the predictive value of age, menopausal status, clinical nodal status, tumour size at diagnosis, oestrogen receptor status, dietary supplementation (L-arginine versus placebo), personality (EPQ-L scores), mood (HADS scores) and a psychological intervention. HADS depression score was a significant independent predictor of pathological response to chemotherapy. HADS anxiety score was a significant independent predictor of clinical response. Because the original tumour size before chemotherapy (also a significant predictor of clinical and pathological responses) was taken into account in the analyses, the results cannot be explained in terms of psychobiological factors related to tumour size. This study supports the importance of psychological factors as independent predictors of response to primary chemotherapy in patients with breast cancer. If they can be replicated, these findings have major implications for the management of women with breast cancer. Psychological factors need to be assessed and evaluated in future trials of chemotherapy.

The Clinical Effectiveness and Cost-Effectiveness of Different Surveillance Mammography Regimens After the Treatment for Primary Breast Cancer: Systematic Reviews, Registry Database Analyses and Economic Evaluation

BACKGROUNDnFollowing primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear.nnnOBJECTIVESnTo identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens.nnnMETHODSnA survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost-utility of differing surveillance regimens.nnnRESULTSnThe majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring >20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was <10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727.nnnLIMITATIONSnFew studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model.nnnCONCLUSIONSnSurveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

Local recurrence in patients with large and locally advanced breast cancer treated with primary chemotherapy

BACKGROUNDnPrimary chemotherapy is being given in the treatment of large and locally advanced breast cancers, but a major concern is local relapse after therapy. This paper has examined patients treated with primary chemotherapy and surgery (either breast-conserving surgery or mastectomy) and has examined the role of factors which may indicate those patients who are subsequently more likely to experience local recurrence of disease.nnnMETHODSnA consecutive series of 173 women, with data available for 166 of these, presenting with large and locally advanced breast cancer (T2>/=4 cm, T3, T4, or N2) were treated with primary chemotherapy comprising cyclophosphamide, vincristine, doxorubicin, and prednisolone and then surgery (either conservation or mastectomy with axillary surgery) followed by radiotherapy were examined.nnnRESULTSnThe clinical response rate of these patients was 75% (21% complete and 54% partial), with a complete pathological response rate of 15%. A total of 10 patients (6%) experienced local disease relapse, and the median time to relapse was 14 months (ranging from 3 to 40). The median survival in this group was 27 months (ranging from 13 to 78). In patients having breast conservation surgery, local recurrence occurred in 2%, and in those undergoing mastectomy 7% experience local relapse of disease. Factors predicting patients most likely to experience local recurrence were poor clinical response and residual axillary nodal disease after chemotherapy.nnnCONCLUSIONSnExcellent local control of disease can be achieved in patients with large and locally advanced breast cancers using a combination of primary chemotherapy, surgery and radiotherapy. However, the presence of residual tumor in the axillary lymph nodes after chemotherapy is a predictor of local recurrence and patients with a better clinical response were also less likely to experience local disease recurrence. The size and degree of pathological response did not predict patients most likely to experience recurrence of disease.

The management of patients with advanced cancer. (III)

In this third article in the series, the management of patients with symptoms arising as a consequence of metastatic disease involving peripheral nerves, the spinal cord and the brain are discussed. In particular, pain, spinal cord compression and symptoms due to either raised intracranial pressure or specific neurological deficits may substantially impair the quality of life in patients with advanced cancer. Pain control, using both medical and surgical treatments, are discussed. The principles underlying the diagnosis and treatment of metastases to the vertebral column and spinal cord, as well as intracranial deposits, are outlined.