1200

transient, sometimes severe, increase in pain ("flare") hasbeen reported shortly after the start of treatment. This effect,which is analogous to that described in the past with

oestrogen therapy, does not necessarily imply disease

progression and can herald a good response to treatment. Onemust be careful not to stop the drug prematurely, thusdepriving a patient of effective treatment. As with otheradditive endocrine treatments, hypercalcaemia mayoccasionally develop, but both this and the flare reaction canbe prevented by the concomitant use of prednisolone, whichalso increases the response rate.’ No benefit derives fromcombining oestrogens or progestagens with tamoxifen,9 butwith androgens’° or cytotoxic chemotherapy" higherresponse rates are observed than with each treatment used

. individually. Unfortunately, the combined treatments havenot yet been compared with sequential use of the

components, so we do not know whether this approachcarries a long-term advantage.The lack of serious side-effects from tamoxifen has

encouraged use of this drug as adjuvant systemic treatmentafter mastectomy for early breast cancer. Preliminary resultsfrom several trials are consistent in showing a prolongation ofthe time to first relapse.12-16 Probably the steroid receptorstatus of the tumour will be shown to be an important factorin influencing the activity of adjuvant endocrine treatment,although conflicting preliminary results prevent firmconclusions at present. Clear advantages of endocrine

therapy over -adjuvant chemotherapy include ease ofadministration and lower subjective toxicity. We do not yetknow what the duration of adjuvant endocrine treatmentshould be, nor whether it simply suppresses tumour growthtemporarily or has a cytotoxic potential capable of eradicatinga population of tumour cells. Furthermore, it is not yet clearwhether the extension of postoperative relapse-free survivalis obtained only at the expense of the effective treatment ofrecurrent and disseminated disease.An argument could now be made that tamoxifen is

indicated for all patients after mastectomy. An extension oftime to first recurrence is likely to be obtained without ill-effect. But not all patients will relapse, many tumours will notbe responsive, and the treatment of subsequent recurrent ormetastatic disease may be compromised. Moreover, we donot know whether unrecognised long-term side-effects mayyet become apparent. The use of tamoxifen as postoperativeadjuvant therapy should still remain under test in clinicaltrials.

7. Plotkin D, Lechner JJ, Jung WE, Rosen PJ. Tamoxifen flare in advanced breast cancerJAMA 1978; 240: 2644-46.

8. Stewart JF, Rubens RD, King RJB, et al. Combination of prednisolone to the primaryendocrine treatment of advanced breast cancer. Eur J Cancer Clin Oncol 1982; 18:1307-14.

9. Mouridsen HT, Palshof T, Rose C. Therapeutic effect of tamoxifen alone versustamoxifen in combination with gestagen and oestrogen in advanced breast cancer.Rec Results Cancer Res 1980; 71: 169.

10 Tormey DC, Lippman ME, Edwards BK, Cassidy JG. Evaluation of tamoxifen doseswith and without fluoxymesterone in advanced breast cancer. Ann Intern Med 1983;98: 139-44.

11. Mouridsen HT, Palshof T, Engelsman E, Sylvester R. CMF versus CMF plustamoxifen in advanced breast cancer in postmenopausal women. An EORTC trial.In: Mouridsen HT, Palshof T, eds. Breast cancer: experimental and clinicalaspects. London. Pergamon Press, 1980: 119-23.

12. Hubay CA, Pearson OH, Marshall JS, et al. Adjuvant therapy of stage II breast cancer:48-month follow-up of a prospective randomized clinical trial. Breast Cancer ResTreat 1981; 1: 77-82.

13. Palshof T. Adjuvant endocrine therapy. Canad J Surg 1981; 24: 379-84.14. Fisher B, Redmond C, Brown A, et al. Treatment of primary breast cancer with

chemotherapy and tamoxifen. N Engl J Med 1981; 305: 1-11.15 Nolvadex Adjuvant Trial Organisation. Controlled trial of tamoxifen as adjuvant agent

in management of early breast cancer: interim analysis at four years. Lancet 1983; i:257-61.

16. Ribeiro G, Palmer MK. Adjuvant tamoxifen for operable carcinoma of the breast:report of clinical trial by the Christie Hospital and Holt Radium Institute. Br Med J1983; 286: 827-30.

HTLV AND AIDS

Dr Tony Andreani and his colleagues end their paper (p1187) by speculating that the tropism of human T-celllymphoma-leukaemia virus (HTLV) for T lymphocytes"makes it a serious candidate as an aetiological factor in somecases of AIDS". Just how serious emerged when on May 19the Paris workers telephoned The Lancet with the news thatappears in an addendum: HTLV-related antigens are

expressed on the blood cells of the AIDS patient described.The May 20 issue of Science carries four reports pointing inthe same direction-an association, no more, betweenretroviruses of the HTLV type and some cases of acquiredimmunodeficiency syndrome (AIDS). Retroviruses haveRNA as their genetic material: the information flowsbackwards to DNA, against the classical tide, and can beincorporated into the host genome.Nobody is saying that HTLV and the AIDS agent are one

and the same. The presence of markers for HTLV could, forexample, indicate just another instance of viral opportunismin patients whose cellular immune defences are

down-indeed that was the reason why Dr Max Essex andcolleagues’ looked for antibodies in AIDS patients and inmatched (and historical) controls. They usedimmunofluorescence against two HTLV lines established incell culture. 25% of patients with AIDS and a similar

proportion of homosexuals with lymphadenopathy, a

possible pre-AIDS state, had antibodies to HTLV. Of 385control sera only 2 or 3 were positive. The other three reportsfocus on more refined virological evidence. By Southern blottechnique, Dr Robert C. Gallo and colleagues2 found

integrated HTLV proviral sequences in 2 of 33 AIDS

patients, both with HTLV antibody. An HTLV virus wasisolated from an American patient with AIDS andtransmitted to umbilical cord blood T cells; and a Haitianwoman and a French female visitor to Haiti, both with AIDS,also expressed HTLV antigen. The fourth report concerns acase of multiple lymphadenopathy rather than fully fledgedAIDS.4Both virus-associated HTL and AIDS are diseases-or

recognitions-of the 1980s, and to suggest that they havesomething in common requires no great feat of imagination.All the same, the clinical connection is far from obvious:HTLV often causes no symptoms and the clinicalmanifestations of AIDS, though broadening all the time, havenot included leukaemia as a major feature. HTLV and AIDSagent have one epidemiological focus in common-the

Caribbean, especially Haiti. However, the other major focus.of HTLV is Japan, from where AIDS has not yet beenreported. Nor has Africa, a possible focus for the AIDS agent,attracted much attention from HTLV researchers. So, to theepidemiological puzzles-why now? and how?-must beadded a third, why there? At least experience with felineleukaemia retrovirus fits: "More cats are killed as a result offeline leukemia virus causing immunosuppression than byfeline leukemia virus causing leukemia".5

1. Essex M, McLane MF, Lee TH, et al Antibodies to cell membrane antigens associatedwith human T-cell leukemia virus in patients with AIDS. Science 1983, 220:859-62.

2. Gelmann EP, Popovic M, Blayney D, et al. Proviral DNA of a a retrovirus, human T-cellleukemia virus, in two patients with AIDS. Science 1983, 220: 862-64.

3. Gallo RC, Sarin PS, Gelmann EP, et al. Isolation of human T-cell leukemia virus macquired immune deficiency syndrome (AIDS). Science 1983; 220: 865-67

4. Barré-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirusfrom a patient at risk for acquired immune deficiency syndrome (AIDS). Science1983; 220: 868-70.

5. Essex M. Cited by Marx JL. Human T-cell leukemia virus linked to AIDS Science

1983; 220: 806-09