Surgical excision has been the method of choice for initial treatment of operable breast
cancer, but is limited in its potential to produce cure. Postoperative systemic therapy
prolongs survival, but kinetics theory and experimental data suggest it may be more
effective if given preoperatively, with the added advantage of leaving the tumour as a
marker of treatment progress. Important questions regarding the efficacy of primary
systemic treatment (PST), its effects on known prognostic indicators, and its influence on
surgical and psychological morbidity remain to be answered. These were addressed in this
171 women aged 27 -69 with operable (T2_31\10.1 M0) breast cancers 31 -85 mm in diameter
were randomised over 68 months, 86 to conventional treatment (CONV) and 85 to PST. In
CONY, surgery was followed by tamoxifen, except for node -positive premenopausal women
who received 6 cycles of cyclophosphamide, methotrexate and 5- fluorouracil. PST was
started after tumour oestrogen receptor (ER) measurement. Patients with ERA 9 fmol /mg
were treated by goserelin if premenopausal or with tamoxifen if postmenopausal. Response
was assessed by weekly examination. Sequential mammography and ultrasound, and
serum CA 15 -3 and HMFG2 measurements were studied as alternative means of
monitoring response. Non responding patients and all patients with ER<20 fmol /mg were
treated with 6 cycles of cyclophosphamide, doxorubicin and prednisolone (CAP). Surgery
followed 12 -16 weeks of PST. The first part of the trial included 79 patients with tumours
>40 mm, all of whom underwent mastectomy. The second part allowed tumours >30 mm,
and breast conservation was an option.
The first 79 patients were studied for morbidity. All toxicity was recorded. Psychological
morbidity was assessed by means of the Hospital Anxiety and Depression, and the Mental
Adjustment to Cancer questionnaires, completed before, during and after treatment.
Surgical morbidity was recorded prospectively according to a pre- defined protocol.
170 evaluable patients have been followed up for a median of 37 months and have
sustained 53 events. No survival difference has emerged. Axillary lymph nodes, ER and
tumour response have emerged as independent indicators of prognosis. Systemic therapy
produced significant changes in tumour characteristics but post treatment prognostic data
was qualitatively similar to conventionally gathered information.
Patients experienced increased anxiety during PST, but psychological adjustment was
similar after completion of all treatment. Despite longer treatment for PST, quality adjusted
survival was identical to that found for CONY. Surgical morbidity was similar for both
Ultrasound proved a highly effective method for measuring tumour size and response to
primary systemic therapy. Tumour marker levels were generally low and did not reflect
The present package of primary systemic treatment is a safe and effective method for
treating operable breast cancer, does not lead to excess morbidity, and offers the
advantages of a response based approach to therapy.