Use Of Adjuvant Systemic Therapy Research Articles

Bone loss and the aromatase inhibitors

The increasing use of systemic adjuvant therapies has considerably improved the prognosis from early breast cancer. However, some of these therapies affect bone metabolism, resulting in osteoporosis. Aromatase inhibitors lower circulating oestrogen levels to almost unrecordable levels in postmenopausal women, predisposing them to bone loss with an increase in fracture risk. Ongoing clinical trials are favouring the use of the aromatase inhibitors over tamoxifen and this may advocate greater use of these drugs in the future. Strategies for the identification and management of treatment-induced bone loss are currently being defined.

The causes and treatment of bone loss associated with carcinoma of the breast

Despite an increasing incidence, the outlook for women with early breast cancer has improved considerably over recent years with a steady fall in the death rate in most western countries. This is due, at least in part, to the widespread use of adjuvant systemic therapy. However, some of these treatments have adverse effects on bone metabolism with increased bone loss which may result in osteoporosis and associated fractures. Most of the effects on bone are mediated by endocrine changes, either induction of an early menopause by chemotherapy and ovarian ablation, or further suppression of postmenopausal circulating oestrogens by aromatase inhibitors. There may also be direct effects of chemotherapy on bone cell function. The pathophysiology of osteoporosis in breast cancer patients, the methods of assessment and treatment options are reviewed. Bone health is a highly topical issue in breast cancer with the emergence of data supporting the use of several years of treatment with aromatase inhibitors. Guidelines on who and how to screen for bone loss, and simple, safe strategies for treatment to prevent osteoporosis are presented.

Radiation Therapy for Invasive Breast Cancer: Not Just for Local Control

Some of the earliest randomized trials in all of clinical medicine, conducted in the1950s, tested theuseof radiation therapy (RT) in patients with invasive breast cancer treated with mastectomy. Subsequently, beginning in the 1960s, trials of breast-conserving surgery combined with RT comparedwithmastectomywerestarted.Over time, considerable information has been accumulated on the use of RT in patients with invasive breast cancer, both after mastectomy and after breast-conserving surgery. In this issue of the Journal of Clinical Oncology, there are three timely reviews by experts in thefieldon the statusofRT in invasivebreast cancer. Two of these reviews summarize the latest information (primarily from randomized clinical trials) on the use of RT aftermastectomy and after breast-conserving surgery. The third review summarizes the latest information on the promising innovative approach of accelerated partial breast irradiation. All the reviews discuss the current state of the art and identify areas of opportunities. There are a couple of major themes in these reviews. One is the important issue of assessing the value of RT separately when used in the absence of, or in conjunction with, adjuvant systemic therapy. Given the demonstrated value of adjuvant systemic therapy in improving relapse-free and overall survival, systemic therapy (hormonal therapy and/or chemotherapy) is now typically used inpatientswith invasive breast cancer. In the absence of systemic therapy, RT reduces local recurrence after either mastectomy or breast-conserving surgery by about 70%. Theoretically, the use of adjuvant systemic therapy by itself might lower local recurrence (lessening the need for RT), interact with RT tomakeRTmore or less effective, and/or provide spatial complementarity (RT for local and systemic therapy for systemic disease) to improve survival when both are used. What has, in fact, been serendipitous, is that these systemic therapies—hormonal therapy more than chemotherapy— interact with RT to substantially improve local tumor control. More important is the finding that RT, when used with systemic therapy, decreases distantmetastases and improves survival. For those of us who grew up in the early ‘‘Fisherian’’ Era (circa National Surgical Adjuvant Breast and Bowel Project Trial B-04), where systemic therapy was not used and RT was found not to influence survival, this new finding is a dramatic one. It suggests that when systemic therapy is effective at controlling micrometastatic disease, it is important to obtain local tumor control. Eventually, it is anticipated that systemic therapy will advance in its effectiveness so that no local therapy is needed; however, until now, the use of systemic therapy has increased the role of local therapy. Of note in theDanish postmastectomy trials testing RT in patients treated with adjuvant systemic therapy, there was about a 30% rate of local recurrence in the absence of RT, and RT resulted in a 10% absolute improvement in survival. If the benefit ofRT is proportional, as is seenwithmost therapies inbreast cancer, and acts through its reduction in local recurrence, it would suggest that patients with a 15% rate of local recurrence would have a 5% absolute improvement in survival. Unfortunately, given the failure to accrue to the large randomized trial of postmastectomy RT in patients with one to three positive nodes treated with adjuvant systemic therapy (a group with an anticipated local recurrence rate of about 15%), this extrapolation remains conjectural. Anothermajor theme in these reviews is theneed tobalance the benefits of RT against its costs, complications, and inconvenience. One of the most serious complications seen withRT for breast cancer, particularly for left-sided cancers, is increased late cardiac mortality. Early techniques of breast cancer RT, especially those techniques which intended to treat the internal mammary nodes, resulted in substantial doses of RT to the heart. It is fortunate that improved RT techniques, especially with the use of computed tomography–based simulation, allow for exclusion of the VOLUME 23 d NUMBER 8 d MARCH 1

Importance of local control in an era of systemic therapy

Diagnostic improvements and earlier detection of tumors have resulted in the emergence of a shift from Halsted paradigm, which has encouraged the use of systemic adjuvant therapy. With these changes in tumor paradigm, the rationale for local treatment as a curative treatment strategy has been challenged. This Viewpoint emphasizes the importance of local control in this scenario.

Improving Outcomes in Advanced Malignant Melanoma

Malignant melanoma continues to increase in incidence throughout the developed world. Surgery remains the cornerstone of curative treatment and the use of adjuvant systemic therapy has provoked much debate. Metastatic disease is incurable in most patients. While combination chemotherapy or biochemotherapy may be considered in certain circumstances, it is now clear that single-agent chemotherapy remains the mainstay of treatment for the majority of patients.A number of new agents and novel approaches are under evaluation and show promise. The pro-apoptotic agent oblimersen has shown improved progression-free survival and response rate, although not overall survival, when combined with dacarbazine compared with dacarbazine alone. The BRaf inhibitor sorafenib (BAY 43-9006) has produced encouraging results when administered with chemotherapy and is now being assessed in randomised studies. Thalidomide in combination with chemotherapy is well tolerated and shows a trend towards increased clinical efficacy compared with chemotherapy alone. Other anti-angiogenic drugs, such as bevacizumab, are being investigated in trials. Results with tumour vaccines have been mixed and several large trials are ongoing. This paper discusses recent pivotal studies and promising new agents in systemic therapy for advanced malignant melanoma.

Best use of adjuvant systemic therapies II, chemotherapy aspects: dose of chemotherapy—cytotoxicity, duration and responsiveness

The overall survival improvement by adjuvant chemotherapy is partly related to patient age, stage and chemotherapy regimens used. Too low dose dose-intensities or total doses will result in inferior outcomes. Conventional dose escalations above standard doses will not be beneficial for doxorubicin or cyclophosphamide, while an epirubicin dose of 90–100 mg/m 2 given every third week in polychemotherapy regimens results in overall survival gains. The issue is more complex, while retrospective analysis of adjuvant regimens have revealed inferior outcomes for patients receiving standard chemotherapy doses and regimens without toxicity. Most cytostatics demonstrate a marked inter-individual variation in different pharmacokinectic parameters, not compensated for by dosage based on body surface area. These facts have partly been the basis for the randomised Scandinavian Breast Group (SBG) studies SBG 9401 and 2000–1, respectively, using tailored dosage strategies aiming at interpatient equivalent dosage. Randomised studies using marrow supported-high dose strategies have so far not been demonstrated to result in overall survival improvements. G-CSF (granulocyte-colony stimulating factor) and dose-dense paclitaxel containing regimens have resulted in a small but significant survival gain compared with conventional three weekly regimens, challenging the present dogma of conventional three–four weekly scheduling, based on normal tissue side-effects rather than tumour biological considerations. The recent microarray based studies demonstrated marked inter-patient variability in gene expression and underline the potential for better patient selection and more tailored therapy strategies.

Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy.

The 1998 St Gallen classification was devised to guide clinicians in the use of adjuvant systemic therapy for women with early breast cancer. In this study, the classification was applied to a historical group of patients with node-negative breast cancer who were treated without adjuvant therapy. The St Gallen classification was applied to 421 women with breast cancer treated with conservative surgery and radiotherapy alone between 1979 and 1994. Primary tumour characteristics were reviewed centrally. When the most stringent version of the St Gallen classification was applied (grade 2 or 3 tumours classified as "high risk"), only 10 per cent of patients were "low risk", with a 10-year distant relapse-free survival (DRFS) rate of 100 per cent, and 15 per cent were at "intermediate risk" (10-year DRFS rate of 94 per cent). The high-risk group (75 per cent of women) had a 10-year DRFS rate of 77 per cent (P < 0.01). If the St Gallen classification had been applied to all patients in this series who were aged less than 70 years, up to 91 per cent would have been recommended to have chemotherapy. The St Gallen classification is an inaccurate measure of prognosis for patients with node-negative breast cancer and should be used with caution.

Ongoing US Cooperative Group Trials Using Taxanes in the Adjuvant Setting

The use of systemic adjuvant therapy in women with early-stage breast cancer has been demonstrated to have a profound impact on survival. The role of paclitaxel and docetaxel in the adjuvant setting has attracted a great deal of attention. Both of these agents are highly active in patients with advanced breast cancer. In addition, they can be utilized in combination with anthracyclines, which have been shown to provide a slightly better outcome in patients with early-stage breast cancer compared to non—anthracycline-containing regimens. Randomized trials have demonstrated a potential role for paclitaxel in adjuvant chemotherapy. In the Cancer and Leukemia Group B 9344 trial, which explored the use of doxorubicin and cyclophosphamide with or without paclitaxel, the initial analysis demonstrated a 22% reduction in the relative risk of relapse and a 26% reduction in the relative risk of death in the paclitaxel group. However, a clear role for the use of paclitaxel in adjuvant therapy remains to be defined. The Breast Cancer International Research Group trial 001 compared the combination of docetaxel/doxorubicin/cyclophosphamide to 5-fluorouracil/doxorubicin/ cyclophosphamide. This trial demonstrated a promising reduction in the relative risk of recurrence of 32% for the docetaxel/doxorubicin/cyclophosphamide group. Ongoing trials will help to further define the role of taxanes in the adjuvant setting for patients with operable breast cancer.

Adjuvant therapy for breast cancer: recommendations for management based on consensus review and recent clinical trials.

Determining the optimal individual adjuvant systemic therapy for breast cancer patients is a challenging undertaking because it requires translating data from clinical trials that have involved thousands of patients into a highly individualized, risk-adjusted approach for the patient at hand. Choosing adjuvant therapy for women with breast cancer includes consideration of four issues: A) evaluation of risk of relapse; B) extrapolation of results from clinical trials; C) therapeutic ratio, and D) the patient's preferences following a thorough discussion with her physician. Data from recently completed phase III adjuvant trials and worldwide consensus conferences document the benefits of adjuvant therapy in improving disease-free survival and overall survival for patients diagnosed with invasive breast cancer >1.0 cm in size. The benefits of hormonal therapy are clear, but limited to patients with estrogen receptor-positive breast cancer. Anthracyclines lead to improved outcomes compared with nonanthracycline regimens. Taxanes appear to improve disease-free survival in patients with node-positive disease, although longer follow-up is required to assess their impact on overall survival. Some countries have reported a reduction in the mortality rate from breast cancer over the past several years. The improved survival rate is due, at least in part, to the use of adjuvant systemic therapy. Ongoing studies are evaluating targeted therapies, with the potential of remarkably improving patient outcome.

Primary breast cancer therapy in six regions of Germany

Studies from six regions of Germany (Aachen (W1), Dresden (E1), Jena (E2), Marburg (W2), Munich (W3), and Stuttgart (C1)) have been compared to verify and assess the quality of healthcare using breast cancer as an example. All of the data collection was carried out in comprehensive cancer centres and is population-based, with the exception of C1. Classic prognostic factors and the initial treatment of 8661 women with breast cancer, diagnosed between 1996 and 1998, were examined. Primary therapy, breast conserving therapy (BCT), and the use of subsequent local radiation and/or systemic therapy (chemotherapy or hormonal therapy) were analysed. BCT was performed on 39.3–57.7% of patients. By pT-category, the proportion of BCT in the six regions were as follows: for pTis between 37.8 and 64.3%, for pT1 between 51.7 and 71.5%, for pT2 between 25.9 and 51.1%, for pT3 between 0 and 13.1% and for pT4 between 0 and 15.2%. Multivariate analyses, adjusted for age and biological factors, showed a significant influence of the treating hospital on the mastectomy rate. The use of radiotherapy after BCT (80%) was quite homogeneous in the six regions. The application of radiotherapy after mastectomy, however, varied between 10.4 and 32.2%. In all regions, for premenopausal patients, the use of adjuvant systemic therapy almost reflected the St. Gallen-Consensus recommendations. In contrast, post-menopausal women with positive lymph nodes were not always treated according to these standards. In all regions, age had an influence on the administration of treatment: elderly breast cancer patients received less BCT, less radiotherapy and less adjuvant therapy than recommended in the St. Gallen-Consensus. Feedback of the results was made available to each hospital, providing a comparative summary of patient care that could be used by the participating hospitals for self-assessment and quality-control.

Options for management of the axillary lymph nodes in breast cancer

Axillary dissection provides important prognostic information and maintains local control in the axilla, but is not generally felt to contribute to the cure of breast cancer. Sentinel node biopsy has the potential to accurately identify node-negative women, allowing axillary dissection to be limited to women with positive nodes who are likely to benefit from the procedure. However, whether complete dissection is needed when a positive sentinel node is identified is uncertain, and this issue is being addressed in a clinical trial. Sentinel node biopsy has also raised the possibility of improving the staging of breast cancer through the detection of micrometastasis. At present, the prognostic significance of small cell clusters detected by immunohistochemistry is uncertain, and definitive information should be forthcoming from ongoing clinical trials. Better stratification of prognostic groups has the potential to allow the more selective use of adjuvant systemic therapy. Axillary dissection provides important prognostic information and maintains local control in the axilla, but is not generally felt to contribute to the cure of breast cancer. Sentinel node biopsy has the potential to accurately identify node-negative women, allowing axillary dissection to be limited to women with positive nodes who are likely to benefit from the procedure. However, whether complete dissection is needed when a positive sentinel node is identified is uncertain, and this issue is being addressed in a clinical trial. Sentinel node biopsy has also raised the possibility of improving the staging of breast cancer through the detection of micrometastasis. At present, the prognostic significance of small cell clusters detected by immunohistochemistry is uncertain, and definitive information should be forthcoming from ongoing clinical trials. Better stratification of prognostic groups has the potential to allow the more selective use of adjuvant systemic therapy.

Economics, quality of life and breast cancer outcomes – is a balance possible?

SUMMARY Breast cancer is a leading cause of cancer death and a major source of healthcare expenditure in most countries in the developed world. Recent therapeutic advances have led to widespread use of breast-conserving therapy and to increased use of systemic adjuvant therapy. New hormonal, chemotherapeutic and supportive care agents have been introduced in the metastatic setting. Collectively, these advances have led to increased survival and, arguably, enhanced quality of life. However, incremental survival benefits have often been small and psychosocial/quality of life improvements difficult to quantify. In contrast, both incremental and total costs have usually been large and readily apparent. Available resources have often been inadequate to provide what is perceived to be optimal care to all patients, and it has been necessary to make trade-offs between survival, psychosocial status/quality of life and costs. Approaches to incorporation of quality of life into economic evaluations are reviewed and limitations discussed. Published economic evaluations in breast cancer are summarized. Potential approaches to balancing costs and benefits, as they apply to breast cancer, are outlined.

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.

Axillary Lymph Node Dissection in Breast Cancer: Current Status and Controversies, Alternative Strategies and Future Perspectives

Axillary lymph node dissection (ALND) has traditionally been considered as a standard procedure in the surgical management of patients with breast cancer. The goals of ALND in breast cancer surgery are: (a) to provide accurate prognostic information, (b) to maintain local control of the disease in the axilla and (c) to provide a rational basis for decisions about adjuvant therapy. Although controversial, ALND may also be associated with a small therapeutic benefit. Recently, the question of whether ALND is needed for every patient with invasive breast cancer has been the subject of ongoing debate in the literature. This is mainly due to the widespread use of adjuvant systemic therapy for patients with node-negative breast cancer and to the increasingly frequent detection of small invasive cancers by mammographic screening; the majority of these patients have negative axillae. Sentinel lymph node (SLN) biopsy is a new, promising, minimally invasive procedure, which accurately predicts nodal status with minimal morbidity, and reserves ALND for patients with positive SLN biopsies. However, this method is still investigational. Partial (levels I and II) ALND remains the gold standard in the surgical management of patients with breast cancer.

From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century

This commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the ‘non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti-oestrogen tamoxifen benefited patients with all stages of the disease. Tamoxifen also reduced the incidence of contralateral breast cancer, as well as tumour in the ipsilateral breast following lumpectomy. The use of preoperative therapy was also found to enhance breast-conserving surgery in women with large tumours, although its value in other circumstances is still being defined. The observation that, as a result of tamoxifen administration, invasive and non-invasive breast cancers can be prevented in women who are at increased risk for such tumours, and the finding that pathological entities such as atypical hyperplasia, lobular carcinoma in situ (LCIS) and intraductal carcinoma (DCIS) can identify women who should be considered candidates for tamoxifen serve as a fitting capstone to the accomplishments of the twentieth century. Breast cancer prevention has now become a reality. Unfortunately, a variety of circumstances have arisen as the result of advances in the understanding and treatment of breast cancer over the last 30 years that threaten to nullify the progress that has been achieved. This distressing phenomenon may be reviewed as a ‘paradox of accomplishment'. The numerous uncertainties, issues and questions that have arisen following the report of each advance in treatment, the surfeit of new information that has not yet been integrated into treatment strategies, the undesirable consequences of enhanced tumour detection, a reversion to Halstedianism and anecdotalism, and the uncertainty of therapeutic decision making resulting from the demonstration of small but statistically significant benefits, particularly in patients with good prognosis, need to be addressed. Inappropriate interpretation of those circumstances threatens to deny women with breast cancer and those at high risk for the disease the opportunity to benefit from treatments that have been proven to be of worth. Perhaps the most important accomplishment of the twentieth century relates to the change in the process of therapeutic decision making. The continued use of the scientific process to test scientifically based hypotheses in well-designed clinical trials must continue if future progress is to be made in the treatment of breast cancer.

Survival and Pattern of Failure Following Locoregional Recurrence of Breast Cancer

This study analyzed prognostic factors at primary diagnosis and at first recurrence for impact on survival after isolated locoregional failure. The aims were: (1) assessment of prognostic factors for time to second locoregional failure, distant failure, and survival in isolated locoregional recurrence of breast cancer after mastectomy; and (2) investigation of the impact of a second locoregional failure on dissemination and survival.Between 1983 and 1985, 99 patients who had undergone mastectomy and then developed isolated local and/or regional recurrences, were treated with radical excision and radiotherapy; none of these patients had distant metastases. Survival and the times to second local failure and distant metastasis were analyzed according to potential prognostic factors.The median follow-up was 123 months; 38 patients were still alive. Median survival was 89 months and the 10-year survival rate was 38%, with no difference between local and regional recurrences. A total of 43 patients developed a second locoregional recurrence after a median of 73 months; primary tumour size and initial node status were significant independent prognostic factors. The annual hazard rates for recurrence were similar for patients developing local failure or systemic recurrence. The 10-year rate of dissemination was 49% for patients with locoregional control, compared with 51% for patients who had a second locoregional recurrence. The prognostic factors for survival were node status at mastectomy and haemoglobin level at first recurrence.The development of a second locoregional recurrence was not associated with an increased risk of dissemination or reduced survival. Differences in prognostic factors for locoregional control and distant metastases suggest that these recurrences represent different biological entities that require different treatment strategies. However, as the achievement of locoregional control had no influence on prognosis, the use of systemic adjuvant therapy may be warranted in a subset of these patients.

Prognostic factors for patients with breast cancers 1cm and smaller.

The widespread use of mammography has resulted in the detection of an increasing number of small invasive breast cancers, i.e. those that are 1cm and smaller. Patients with these small cancers generally have a low incidence of axillary lymph node metastases, and this has led some to question the routine use of axillary dissection in these patients. In addition, the prognosis of these patients is generally favorable, and the routine use of adjuvant systemic therapy is difficult to justify. Nonetheless, some patients with these small invasive cancers will have axillary nodal involvement and/or develop metastatic disease. The identification of this prognostically unfavorable subset of patients within this otherwise favorable group is an important goal of clinical research. In this article, we review the available literature on prognostic factors for patients with breast cancers 1cm and smaller to help determine which of these features might be of value in the identification of patients at risk for axillary lymph node involvement and/or metastatic disease.

Carcinoma of the breast in males: a multiinstitutional survey.

Breast carcinoma in males is infrequent, and information regarding the results of modern treatment is limited. Cases of breast carcinoma in males were accrued from multiple hospitals in one region to determine treatment, survival, and prognostic factors. A retrospective review was performed of 217 cases of breast carcinoma in males accessioned at tumor registries of 18 health care institutions in eastern Wisconsin between 1953 and 1995. Of the 217 cases, 215 (99.1%) were carcinomas. The majority of carcinomas were of invasive ductal type and presented as masses. Carcinoma in situ accounted for 5.5% of cases. The 5- and 10-year observed survivals for men were 50.6% and 23.7%, respectively. A high rate of post-treatment mortality from comorbid disease was found. Stage, axillary lymph node status, number of lymph nodes with metastases, and tumor hormone receptors were significant indicators of prognosis. Adjuvant systemic chemotherapy and hormone therapy improved the prognosis of patients with axillary lymph node metastases and hormone receptor positive tumors. Earlier stage at presentation and improved 5-year survival were found in cases occurring between 1986-1995 compared with those occurring in earlier years. Use of modified radical mastectomy and systemic adjuvant therapy also increased since 1986. The clinical, pathologic, and prognostic features of breast carcinoma in men are similar to those reported for women. The poorer prognosis of men is related to older age at diagnosis, more advanced stage of disease at presentation, and high mortality from comorbid disease. Earlier diagnosis, less radical surgery, and use of systemic adjuvant therapy are coincident with an improved prognosis for men.

Variations in the management and survival of women under 50 years with breast cancer in the South East Thames region.

A retrospective, population-based study was undertaken to determine variations in the management of women aged less than 50 years with primary breast cancer in different hospital settings and the influence of these variations on survival. A total of 1757 women who were resident in the South East Thames Health Region aged less than 50 years at the time of diagnosis of breast cancer and who presented during a 5 year period (January 1984 to December 1988) were recorded by the Thames Cancer Registry. The hospitals at which primary surgery was undertaken were categorised as teaching or non-teaching hospitals. The non-teaching hospitals were grouped according to the mean number of patients treated annually during the study period (< or = 2, 3-9, > or = 10 each year). The following factors were compared between these groups: age, extent of disease, tumour morphology, extent of primary surgery (mastectomy vs less than mastectomy), use of axillary surgery (any vs none) and use of systemic adjuvant therapy. Survival rates for the different groups were compared. Registration rates did not differ significantly between health districts. A total of 1485 (85%) women underwent surgery in over 90 different hospitals. In 1324 (86%) of these cases the surgery was undertaken in a total of 42 NHS hospitals within SE Thames Health Region or in seven teaching hospitals in adjacent regions. Mastectomy rates decreased from 52% in 1984 to 28% in 1988 (P<0.0001), but were consistently higher in teaching hospitals (P=0.01). The use of any form of axillary surgery decreased from 49% to 36% over the 5 year period (P=0.003), with significantly lower rates of axillary surgery being performed in non-teaching hospitals (P<0.0001). The proportion of cases recorded as having non-specific morphology was higher in nonteaching than in teaching hospitals (P<0.0001). On multivariate analysis survival was significantly (P<0.001) influenced by stage and tumour histology. Among patients who underwent surgery, the type of hospital in which this was undertaken did not appear to influence survival significantly. This analysis of routine cancer registry data indicates that patients were widely dispersed in a large number of different hospitals and that there were marked variations in practice according to the type of hospital to which patients presented. The treatments provided were frequently at variance with those recommended at a consensus conference held during the study period, particularly in relation to the use of axillary surgery and adjuvant systemic therapy. The way in which services are currently provided may hamper the delivery of appropriate management and comprehensive support. These data thus have implications for the purchasing and provision of services for this common condition.

Cervical metastasis of occult origin—Treatment options and outcome

Ninety one patients with metastases of unknown origin in cervical nodes seen between 1986 and 1990 were respectively analysed. Majority of the patients (58%) presented with a nodal mass of more than 6 cm size. Jugulodigastric node was the commonest site of involvement seen in 74%, 76% and 69% of patients who presented with single node, multiple ipsilateral nodes and bilateral nodes respectively. Two year disease free survival (DFS) was 17% with radical radiotherapy alone and 48% with combined radiotherapy and radical neck dissection. Overall 2 year DFS with N1, N2and N3 disease were 100%, 35% and 14% respectively, with combined therapy offering better results in patients with a nodal size of more than 3 cm. 14% of the patients who received curative therapy developed a primary, with a majority (10%) within the field of irradiation. Use of combined surgery and radiation, successful salvage of locoregional failures and possibly use of adjuvant systemic therapy would result in improved DFS in patients with advanced nodal disease.