title: Markers of biological variation of breast cancer
Creators: name: Campbell, Frederick Charles
Publisher: name: University of Glasgow
Year: 1983
Subjects: subject: Oncology.

description: Our comprehension of the biological nature of breast cancer is obscure, despite generations of organised research. Clinical experience emphasises that this disease has a variable range of malignancy with different clinical manifestations and prognosis. One in fifteen women in the United Kingdom develops breast cancer and the majority of these die as a result of it. Primary treatment methods which are based upon anatomical or physical considerations, have been applied in a blanket fashion but have failed to achieve any Improvement of mortality rates. A more specific primary treatment, appropriate to an individual situation and outlook could be provided if accurate markers of the range of malignancy in breast cancer were available. Attempts to define 'biological markers' within the primary growth which might shed some light upon its innate nature and possibly distinguish a favourable from an unfavourable type have met with limited success in recent years. The Nottingham-Tenovus Study of primary breast cancer, under the direction of Professor Roger Blarney has been at the forefront of these developments. Data from this centre have shown that oestrogen receptor status and histological grade of primary breast cancer are inter-related and each variable also bears some relationship to prognosis. However, studies of these 'intrinsic' prognostic variables remain at a preliminary stage. Many intrinsic variables have been identified, many are inter-related but their precise clinical applications have not been defined. It is known that many aspects of tumour behaviour have an influence upon prognosis but, to date we have been unable to isolate an ideal 'intrinsic marker' for any specific tumour characteristic. This thesis describes a search for factors in the primary cancer which will identify specific tumour characteristics and allow accurate prediction of the likely clinical course in individual patients. During a two year interval from August 1980, I was privileged to hold the Tenovus Research Fellowship in Nottingham and I was involved in every aspect of investigation and management of patients which these studies concern. I personally carried out most mastectomies and lymph node biopsies and thus I harvested and distributed all specimens. Histological grading of primary cancers and examination of lymph node biopsies for metastatic tumour were carried out independently by Dr. C.W. Elston and Dr. Jane Johnson. Steroid receptors were measured in primary cancers by the Tenovus Institute for Cancer Research in Cardiff under the direction of Professor Keith Griffiths. As Tenovus Research Fellow I harvested, prepared and frequently transported tumour specimens in liquid nitrogen to Cardiff and carried out some receptor assays. I carried out all prostaglandin E2 radioimmunoassay's in tumour explants, in the Department of Surgery, Queen's Medical Centre, Nottingham. I also personally carried out all cellularity counts in histological sections of cancers in which prostaglandins were measured. Clinical follow up of patients after mastectomy continued in the Nottingham Post Mastectomy Clinic, which I conducted. I scrupulously documented all important 'events' in the 'Master Index' and later summarised the index to allow its transfer on to computer. I carried out a clinical examination and a full range of investigations on detection of recurrence in all patients. I designed and used detailed proformas to allow (a) documentation of the precise dimensions and distribution of secondary disease before endocrine treatment, (b) clinical follow up with accurate documentation of any change in target metastases. These proformas are now complete on more than two hundred patients and make up the Nottingham Advanced Breast Cancer File. I personally supervised treatment at the Advanced Breast Cancer Clinic and arranged external review for assessment of response to endocrine therapy. I carried out all statistical analyses although I received much valuable help from Dr. John Hayblttle. By these methods, intrinsic parameters in primary breast cancer were related to the clinical events which determine prognosis, in women in the Nottingham-Tenovus Study.