An objective biochemical assessment of therapeutic response in metastatic breast cancer: a study with external review of clinical data.

A series of tumour related markers have been examined in 179 patients receiving primary endocrine therapy for metastatic breast cancer. Significant correlations between therapeutic response (UICC criteria after 6 months of treatment) and appropriate alterations in serum concentrations of carcinoembryonic antigen, ferritin, c-reactive protein, orosomucoid and the erythrocyte sedimentation rate, have been observed when changes in these markers were examined only at high serum concentrations. By combining these five markers a 'therapeutic index' of response has been devised which can be employed at an early stage of treatment in more than 90% of patients, giving an overall sensitivity/specificity of 90%/78% for therapeutic response or disease stabilisation over a 6-month period. The design of an objective measurement of response, which is easy to perform, has the potential to replace the existing, largely subjective. UICC criteria for retrospective judgement of response, and may also be used to direct systemic endocrine therapy

Potential for cost economies in guiding therapy in patients with metastatic breast cancer.

Therapeutic response in patients with advanced breast cancer is conventionally assessed with reference to criteria devised by the International Union Against Cancer. Evidence to date suggests, however, that assessments of equivalent quality may be obtained at lower cost from the use of serum markers. The paper presents estimates of potential cost savings resulting from the use of serum markers in place of conventional assessment and argues that the size of these savings merits the establishment of a randomised controlled trial

The use of an LH-RH agonist (ICI 118630, Zoladex) in advanced premenopausal breast cancer.

Fifty-three premenopausal patients presenting with advanced breast cancer have been treated with a potent new luteinising hormone-releasing hormone agonist Zoladex (ICI 118630) in a phase I clinical trial. On progression of disease 26 patients have undergone therapeutic oophorectomy. We present the clinical and endocrinological responses to treatment in 45 assessable patients. The response rate to Zoladex in this series was 31% and the ER status of the primary tumour was predictive of a response to the luteinising hormone-releasing hormone

Oestrogen-receptor status and sites of metastasis in breast cancer.

The oestrogen receptor (RE) status of the primary tumour has been assessed in 466 of a consecutive series of 550 patients with primary operable breast cancer. All patients were followed up (without treatment) until the development of recurrence or metastases. Distant metastases have so far occurred in 124 patients and 82 have had symptomatic local or regional recurrence. A significant correlation exists between the RE status of the primary tumour and subsequent patterns of metastasis. Symptomatic metastases to regional lymph nodes are more common with RE- cancers. There is no significant difference in either time of onset or total incidence of distant metastases between patients with RE+ and RE- tumours. Distribution of distant metastases is influenced by RE status: RE+ tumours tend to recur in bone, RE- tumours show affinity for viscera

Relationship between oestrogen-receptor content and histological grade in human primary breast tumours.

A series of 300 patients presenting consecutively with primary operable breast cancer has been studied. A significant correlation was found between oestrogen-receptor (ER) content and histological grade: the better-differentiated tumours rarely lacked receptor. This correlation was significant only in women defined as post-menopausal. Data on early recurrence of disease indicate a worse prognosis for women in whom primary tumours are ER-

Thymidine kinase in breast cancer.

The enzyme thymidine kinase is associated with DNA synthesis. Thymidine kinase serum levels were studied in normal controls (n = 20), patients with primary breast cancer (n = 60), patients with systemic breast cancer (n = 20) and as a non-cancer disease control group in patients with inflammatory gastrointestinal disorders (n = 20). Comparison of pretreatment values in the cancer patients with the normal controls showed a significant difference between the three groups in relation to stage of disease: mean values 4.22 (+/- 1.08), 6.22 (+/- 2.24) and 9.79 (+/- 7.56) pmol ml-1 h-1 for normal controls, operable breast cancer and systemic breast cancer respectively (P less than 0.005; analysis of variance). Patients with systemic breast cancer had a significantly elevated serum thymidine kinase level compared to controls (P less than 0.01) and patients with primary operable cancer (P less than 0.05). Patients with primary operable cancer had significantly higher serum thymidine kinase levels over normal controls (P less than 0.01). Mean serum TK in patients with inflammatory gastrointestinal diseases was similar to normal controls but significantly less than both patients with primary operable breast cancer and patients with systemic breast cancer. Twenty patients with operable breast cancer were followed up after primary surgery by serial 3-monthly thymidine kinase levels in the disease free interval. Four patients have developed systemic recurrence with a rise in the mean thymidine kinase value to 14.3 pmol ml-1 h-1. Ten patients with advanced breast cancer had serial thymidine kinase levels measured 2-monthly during the first 6 months of primary hormone therapy. The serum values fell in all five responders (mean 9.12-4.78 pmol ml-1 h-1) and rose in all five progressors (mean 8.62-38.5 pmol ml-1 h-1). Serum thymidine kinase reflects stage of disease in breast cancer. Serial thymidine kinase levels in patients with systemic breast cancer reflected response to systemic therapy

Ki67 immunostaining in primary breast cancer: pathological and clinical associations.

Ki67 immunostaining has been performed on 136 primary breast cancers and related to various clinical and pathological features of the disease. Staining was most frequently seen in poorly differentiated tumours showing high rates of mitotic activity, but was independent of tumour size, lymph-node status and ER expression. A high level of Ki67 immunostaining was often associated with early recurrence of breast cancer after mastectomy. These data are consistent with the concept of the Ki67 antibody detecting an antigen that is closely related to cell proliferation and thus provides a clinically useful marker for this important characteristic of the tumour

A prognostic index in primary breast cancer.

From a multiple-regression analysis of prognostic factors and survival in a series of 387 patients with primary breast cancer, a prognostic index has been constructed, based on lymph-node stage, tumour size and pathological grade. This index is more discriminating than lymph-node stage alone, and enables a larger group of patients to be identified with a very poor prognosis