MD, FRCS, FRCRMeyerstein Institute of Oncology and Academic Department of Surgery, University College London Hospitals NHS Trust,London, UKIn Time magazine’s extensively researched breast cancerissue (June 10, 2002), one particular quote had a specialresonance for us. In the introduction to a remarkablycomprehensive article, Dr Julie Gralow, an Oncologist atthe Fred Hutchinson Cancer Research Centre in Seattle,stated ‘‘We may be far overtreating our patients… We’venow got women being diagnosed with tumours that wouldprobably never have been treated if we didn’t havemammography. They probably would have lived long,natural, healthy lives never knowing they had breastcancer’’ (J Gralow, quoted in [1]).For some years it has been apparent that, for manypatients, powerful treatment by surgery (even when limitedto tumour excision with breast preservation) together witha 6 week programme of radiation therapy may be morethan sufficient. We already know a good deal (althoughnot of course enough) about the profile of a typical breastcancer patient with low risk of local and distant recur-rence: a small, low or moderate grade tumour, surgicallycompletely excised, positive for oestrogen and/or proges-terone receptors, negative for HER2 and with negativeaxillary nodes. Post-menopausal patients clearly have alower incidence of local recurrence; for example, in thelarge study by Bartelink et al [2], patients over the age of60 years had a rate of local recurrence following 50 Gywhole breast radiation of only 4% (without an additionalboost), the rate reducing still further to 2.5% with anadditional 16 Gy given by electron beam therapy. Forpatients aged 41 to 50 years, the rates were 9.5% and 5.8%,respectively (median follow-up 5.1 years). What’s more, anever increasing number of patients now present with smalltumours (,1 cm) identified on mammographic screening,of whom approximately three-quarters will have oestrogenreceptor (ER)/progesterone receptor (PR) positive tumours,for which targeted hormone therapy with tamoxifen offerssustained long-term benefit for both local and distantrelapse [3, 4]. Using a well tolerated oral aromataseinhibitor such as Anastrazole reduces the risk still further(for both local and distant relapse), also, incidentally,reducing by three-quarters the risk of development of acontralateral primary breast cancer [5].For all these reasons, we strongly support Gralow’sview. Even in younger women known to be at higher riskof relapse, including those with axillary node-positivedisease, the use of systemic adjuvant cytotoxics sharplyreduces the risk of recurrence [3, 4, 6]. For hormonereceptor-positive patients, i.e. the large majority, adjuvanthormone therapy as well as surgical or medical oophor-ectomy all add further benefit [2–4, 6].What is the consequence of Gralow’s observation? Inthe past, it has been regarded as mere flight of fancy toimagine that we can identify patients at such low risk ofrecurrence that a less intensive form of treatment thanlocal surgical excision followed by whole breast irradiationcould be regarded as ‘‘adequate’’. In this sense, thisgeneral policy remains little different in principle from theequally compelling (in its day) policy of radical, then lessdamaging forms of mastectomy – although admittedly,using local excision, breast preservation and post-operativeradiotherapy is generally regarded as more ‘‘humane’’ eventhough attempts at demonstrating an improved quality oflife have been largely elusive [7]. None the less, theevolving history of local treatment for early breast cancerhas centred on an ever increasing recognition of theimportance of breast conservation for body image andcosmesis, an essential requirement for most women. Thishas largely been achieved by the increasing acceptance ofbreast-conserving surgery with post-operative radiotherapy[8]. Yet despite this ready acceptance, recent data from theworld’s largest ever randomized breast cancer study, withexcellent quality control and a high level of expertise,confirm a mastectomy rate approaching 50% [ATACTrialists Group, unpublished data].We believe that the time has come to move on further.For many patients, particularly those presenting over theage of 50 years with small, low grade, ER positive, axillarynode negative tumours, it is surely right to question thenecessity of a lengthy and sometimes damaging course ofradiation therapy. Radiation oncologists who are totallysatisfied with their often excellent cosmetic results and lowrelapse rates following standard treatment should bearin mind the work of the Oxford-based Early BreastCancer Trialists’ Collaborative Group, namely that despitea lower breast cancer cause-specific death rate in irradiatedpatients, the increased mortality for other non-cancercauses wipes out this advantage [9]. The assumption thatthe excess non-cancer-related deaths in this large meta-analysis were due essentially to reliance on older outmodedradiation techniques may be correct – but it remains anassumption only, and considerable additional data attestto the cardiac, pulmonary and neurological dangers ofwhole breast irradiation [10–12]. Moreover, the use ofanthracycline-based chemotherapy regimens apparentlyincreases some of these risks still further [13].
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May 1, 2005
L W Cuttino + 2
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