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TREATMENT OF BREAST CANCER—IS CONSERVATION SAFE?
964
initial EEG is a poor indicator of prognosis in infantile spasmslO,11 and febrile convulsions.8,9 Abnormality of background activity may be an adverse feature,6 and subsequent epilepsy and mental retardation may be associated with initial EEG abnormality of patients in the status or "other" groups.’l Common prognostic factors are thus hard to discern in epileptic syndromes appearing in the first year of life. Overall the outlook is best after febrile convulsions; subsequent epilepsy is most likely in the status and "other" groups; and the most intractable types of epilepsy arise after West syndrome and status. Onset in the first 6 months of life carries a particularly poor prognosis. Recurrence of seizures in the first year may be associated with subsequent epilepsy in the febrile-convulsion, status, and "other" groups. As in the "other" group, children with infantile spasms are at greatest risk if the onset is early and if before the first seizure their development has been abnormal and they have shown a neurological or intellectual deficit. In all symptomatic seizures the outlook is bad: they tend to arise in the first 6 months and to be associated with other features (perinatal damage, neurological abnormality, retarded development) that are gloomy features in epilepsy arising at any age. Factors associated with a good prognosis are cryptogenic seizures starting after the age of 6 months in a child whose physical and mental development has been normal, who has had infrequent brief and generalised seizures, who had a normal initial EEG, and who has a family history of epilepsy.
TREATMENT OF BREAST CANCER—IS CONSERVATION SAFE? LOCALISED resectable breast cancer can be treated in many ways-surgery, radiotherapy, systemic treatment. Surgery can range from biopsy alone to extensive operations in which the whole breast, underlying muscles, axillary contents, and internal mammary nodes are removed. Radiotherapy may be used as an adjunct to surgery or be the primary treatment, when it may involve external beam treatment, insertion of radioactive implants, or both. As for systemic therapy, there
approaches-endocrine treatments (ablative or additive), cytotoxic drugs (single or multiple), immunotherapy, or combined treatments. Hence, the present are numerous
confusion about the best treatment for this disease is understandable. No one knows for certain the right treatment for an individual patient. Fortunately, many patients are treated in clinical trials and, gradually, answers are emerging which will allow us to treat this disease with greater confidence in the future. The objectives of surgical treatment are several. The main hope is that the tumour can be resected entirely and "cure" achieved. The resected tissue also provides important information (histological and biochemical) which assists in the selection of adjuvant treatment and the planning of treatment later on for recurrent disease. The achievement of local control by effective surgery, even if distant metastases do occur, makes an important contribution to the quality of life. But, for a century, surgical treatment has usually meant removal of the whole affected breast and so our objectives have been achieved only at the expense of distressing
mutilation. Now attention is being given to techniques that conserve unaffected breast tissue, to give an acceptable cosmetic result without compromising the other objectives of treatment.
Fisher et all conclude that "segmental" mastectomy with irradiation is suitable for breast tumours no larger than 4 cm in diameter, provided that the excised specimen has tumourfree margins and that patients with involved axillary nodes
given adjuvant chemotherapy. Segmental mastectomy is resection of the tumour with enough normal tissue to ensure that the specimen margins are tumour-free. They randomly allocated 2163 patients to have either total (simple) are
mastectomy or segmental mastectomy, or segmental mastectomy followed by irradiation of the residual breast,
overlying skin, underlying muscle, and draining lymphatics. All patients had an axillary dissection and those with involved nodes received adjuvant chemotherapy with a combination of melphalan and 5-fluorouracil. As expected, radiation significantly reduced the appearance of recurrent tumour in the ipsilateral breast after segmental mastectomy (7’7% versus 27’ 9% at 5 years). This reduction was most striking in patients with axillary node involvement, the implication being that adjuvant chemotherapy contributed to this lower recurrence rate. Loco-regional recurrence in the skin and lymph nodes was significantly reduced by irradiation. This confirms the findings of an earlier trial by the same group in which radical mastectomy and total mastectomy (with or without radiation) were compared.Distant recurrence rate and survival were similar for all treatments in both trials. The conservation trial, scrupulously conducted and reported in clear detail, is not free from difficulties in interpretation. Patients allocated to receive segmental mastectomy had a total mastectomy if tumour was present at the margins of the segmental specimen (10% of this group), but in the analysis these patients were included with those having had a segmental mastectomy. Further, 15% of the patients enrolled in the trial were excluded (largely because many refused the allocated treatment), and this led to considerable disparity in the numbers within each treatment group. Finally, it is widely accepted that long follow-up is needed in trials for early breast cancer, but here the mean duration of follow-up was just 39 months, only 13% of the patients being at risk at 5 years. This trial supports the view that breast conservation for small tumours is no worse than mastectomy in terms of distant recurrence rate or survival. However, information has not been given on morbidity from recurrence in the breast or on the precise cosmetic results from segmental mastectomy. The results are interpreted as giving no support to radiation boosts at the excision site, but such boosts may be important if less than segmental resection is used in an attempt to achieve the best possible cosmetic result. Furthermore, the trial patients received a total mastectomy if tumour was present at the margin of the segmental specimens. Perhaps the need for this could have been obviated by appropriate radiation boosting. Finally, we need to identify those patients at high risk for recurrence after conservation surgery. Possibly, a large in-situ cancer component which might be radioresistant could predispose to recurrence, rendering breast conservation unsuitable. These questions are now being addressed in British and European trials and firm answers can be expected in time. 1. Fisher
B, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomywith orwithout radiation inthe treatmentof breast cancer. N Engl J Med 1985; 312: 665-73. 2 Fisher B, et al Ten-year results ofa randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation N Engl J Med 1985; 312: 674-81.
initial EEG is a poor indicator of prognosis in infantile spasmslO,11 and febrile convulsions.8,9 Abnormality of background activity may be an adverse feature,6 and subsequent epilepsy and mental retardation may be associated with initial EEG abnormality of patients in the status or "other" groups.’l Common prognostic factors are thus hard to discern in epileptic syndromes appearing in the first year of life. Overall the outlook is best after febrile convulsions; subsequent epilepsy is most likely in the status and "other" groups; and the most intractable types of epilepsy arise after West syndrome and status. Onset in the first 6 months of life carries a particularly poor prognosis. Recurrence of seizures in the first year may be associated with subsequent epilepsy in the febrile-convulsion, status, and "other" groups. As in the "other" group, children with infantile spasms are at greatest risk if the onset is early and if before the first seizure their development has been abnormal and they have shown a neurological or intellectual deficit. In all symptomatic seizures the outlook is bad: they tend to arise in the first 6 months and to be associated with other features (perinatal damage, neurological abnormality, retarded development) that are gloomy features in epilepsy arising at any age. Factors associated with a good prognosis are cryptogenic seizures starting after the age of 6 months in a child whose physical and mental development has been normal, who has had infrequent brief and generalised seizures, who had a normal initial EEG, and who has a family history of epilepsy.
TREATMENT OF BREAST CANCER—IS CONSERVATION SAFE? LOCALISED resectable breast cancer can be treated in many ways-surgery, radiotherapy, systemic treatment. Surgery can range from biopsy alone to extensive operations in which the whole breast, underlying muscles, axillary contents, and internal mammary nodes are removed. Radiotherapy may be used as an adjunct to surgery or be the primary treatment, when it may involve external beam treatment, insertion of radioactive implants, or both. As for systemic therapy, there
approaches-endocrine treatments (ablative or additive), cytotoxic drugs (single or multiple), immunotherapy, or combined treatments. Hence, the present are numerous
confusion about the best treatment for this disease is understandable. No one knows for certain the right treatment for an individual patient. Fortunately, many patients are treated in clinical trials and, gradually, answers are emerging which will allow us to treat this disease with greater confidence in the future. The objectives of surgical treatment are several. The main hope is that the tumour can be resected entirely and "cure" achieved. The resected tissue also provides important information (histological and biochemical) which assists in the selection of adjuvant treatment and the planning of treatment later on for recurrent disease. The achievement of local control by effective surgery, even if distant metastases do occur, makes an important contribution to the quality of life. But, for a century, surgical treatment has usually meant removal of the whole affected breast and so our objectives have been achieved only at the expense of distressing
mutilation. Now attention is being given to techniques that conserve unaffected breast tissue, to give an acceptable cosmetic result without compromising the other objectives of treatment.
Fisher et all conclude that "segmental" mastectomy with irradiation is suitable for breast tumours no larger than 4 cm in diameter, provided that the excised specimen has tumourfree margins and that patients with involved axillary nodes
given adjuvant chemotherapy. Segmental mastectomy is resection of the tumour with enough normal tissue to ensure that the specimen margins are tumour-free. They randomly allocated 2163 patients to have either total (simple) are
mastectomy or segmental mastectomy, or segmental mastectomy followed by irradiation of the residual breast,
overlying skin, underlying muscle, and draining lymphatics. All patients had an axillary dissection and those with involved nodes received adjuvant chemotherapy with a combination of melphalan and 5-fluorouracil. As expected, radiation significantly reduced the appearance of recurrent tumour in the ipsilateral breast after segmental mastectomy (7’7% versus 27’ 9% at 5 years). This reduction was most striking in patients with axillary node involvement, the implication being that adjuvant chemotherapy contributed to this lower recurrence rate. Loco-regional recurrence in the skin and lymph nodes was significantly reduced by irradiation. This confirms the findings of an earlier trial by the same group in which radical mastectomy and total mastectomy (with or without radiation) were compared.Distant recurrence rate and survival were similar for all treatments in both trials. The conservation trial, scrupulously conducted and reported in clear detail, is not free from difficulties in interpretation. Patients allocated to receive segmental mastectomy had a total mastectomy if tumour was present at the margins of the segmental specimen (10% of this group), but in the analysis these patients were included with those having had a segmental mastectomy. Further, 15% of the patients enrolled in the trial were excluded (largely because many refused the allocated treatment), and this led to considerable disparity in the numbers within each treatment group. Finally, it is widely accepted that long follow-up is needed in trials for early breast cancer, but here the mean duration of follow-up was just 39 months, only 13% of the patients being at risk at 5 years. This trial supports the view that breast conservation for small tumours is no worse than mastectomy in terms of distant recurrence rate or survival. However, information has not been given on morbidity from recurrence in the breast or on the precise cosmetic results from segmental mastectomy. The results are interpreted as giving no support to radiation boosts at the excision site, but such boosts may be important if less than segmental resection is used in an attempt to achieve the best possible cosmetic result. Furthermore, the trial patients received a total mastectomy if tumour was present at the margin of the segmental specimens. Perhaps the need for this could have been obviated by appropriate radiation boosting. Finally, we need to identify those patients at high risk for recurrence after conservation surgery. Possibly, a large in-situ cancer component which might be radioresistant could predispose to recurrence, rendering breast conservation unsuitable. These questions are now being addressed in British and European trials and firm answers can be expected in time. 1. Fisher
B, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomywith orwithout radiation inthe treatmentof breast cancer. N Engl J Med 1985; 312: 665-73. 2 Fisher B, et al Ten-year results ofa randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation N Engl J Med 1985; 312: 674-81.