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J Intern Med. 1998 Sep;244(3):189-98.

Survival in breast cancer patients after the first episode of hypercalcaemia.

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Department of Oncology, Copenhagen University Hospital, Denmark.



To investigate hypercalcaemia (serum ionized calcium (S-Ca2+) > 1.35 mmol L(-1)) in breast cancer patients before and after the introduction of bisphosphonates and the effect of disease- and treatment-related factors on survival.


Prospective and retrospective registration of covariates.


A department of oncology in a university hospital.


A consecutive cohort of 212 hypercalcaemic patients never treated with bisphosphonate was identified prospectively (period 1) and 193 patients with metastases were classified into three groups: mild (S-Ca2+ < 1.48: n=102). moderate (1.48 < or = S-Ca2+ < or = 1.60; n=41). and severe hypercalcaemia (S-Ca2+ > 1.60 mmol L(-1); n=50). Fifty-one patients with severe hypercalcaemia all treated with bisphosphonate except one were identified retrospectively (period 2).


For period 1 median survival was 6.7 months. Survival was significantly decreased in the two groups with the highest initial S-Ca2+ (P < 0.0001). Median survival times in severely hypercalcaemic patients from periods 1 and 2 were 1.4 (9 5(% confidence interval 0.8-2.1) and 2.2 (95% confidence interval 1.3-3.1) months, respectively. In a Cox model for period 1 significant covariates were: WHO performance, extent of metastases, whether systemic anticancer treatment could be given, and haemoglobin, but not S-Ca2+.


Prognosis is poor in hypercalcaemic breast cancer patients with WHO performance 3-4 and advanced metastatic disease when effective systemic treatment can no longer be offered. Bisphosphonate treatment does not seem to improve survival in severe hypercalcaemia. Antihypercalcaemic treatment of mild malignancy-associated hypercalcaemia appears not to be vital. Therapeutic efforts should be aiming at patients with moderate hypercalcaemia.

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