Background: Research on breast cancer (BC) has shown numerous cases of hypercalcemia with a high PTH level, meaning the hypercalcemia was not due to the physiological bone metastasis complication, but instead due to a concomitant primary hyperparathyroidism (pHPT). Since then, some studies have tried to reveal a possible link between BC and pHPT. However, most of the findings are not definitive and such an association cannot be formally established. Our aim was to evaluate a potential association between these two diseases in a population centred at the CHUV Hospital, in Lausanne, Switzerland.
Methods: All patients who were surgically treated for pHPT or BC at CHUV between 2002 and 2020 were included in the study. A crossover group with patients who were treated for BC and pHPT was obtained. Different variables were extracted from our electronical database, such as demographic factors, biological markers and pHPT/BC histopathological characteristics. We compared the variables between each group and a control group. Since a fixed control group could not be obtained, we considered such a group according to the variable being compared (for example, the reference values of the CHUV laboratory for the comparison of biomarkers). Comparative analysis were performed using the chi-square test for discrete variables and sample t-test for continuous variables.
Results: A total of 4953 patients were listed in the initial data base. Patients treated for pHPT formed group 1 (n=430) and those for BC formed group 2 (n=4523). The crossover group (group 3) formed a sample of 16 female patients (0.35%, mean age 64.75 years). The age at diagnosis did not show any significant difference between the first and third group (60.76 years, SD 15.77; 64.75 years, SD 11.77). For biomarkers, boxplots and mean values showed statistical difference between group 1 and 3 in PTH and calcium (p-value=0.01 for both comparisons). These results should be viewed with caution, given the small number of patients in group 3, a very narrow confidence interval for calcium, and some PTH values in the extremities distorting the distribution. BC histopathological subtypes and pHPT etiologies incidence were similar in the crossover group to the expected incidence in global population. The date of diagnosis for pHPT preceded the one for BC in 75% of the cases, but without any statistically significant difference (p-value=0.08, chi-square test for a proportion of 50%). Lastly, among the patients with BC (n=4523), 16 had also pHPT, 353.7/100000 patients. Comparing with the incidence rate of pHPT in the swiss population, it showed a statistically significant difference. Our study incidence was 3 times greater than the highest incidence for each group age in the swiss population (p-value=0.00012, chi- square test for a proportion). Similarly, BC incidence in our study revealed it was 10 times higher than the highest incidence rate of BC in Switzerland for each age category (p-value<2e-16, chi-square test for a proportion).
Conclusion: Considering our small sample of patients in the crossover group and our comparative analysis results, we cannot conclude on an association between pHPT and BC. Other studies had stronger results and pHPT should be considered as a possible cause of hypercalcemia in patients with non-aggressive breast cancer. We recommend that all BC patients with elevated serum calcium levels, even those without evidence of metastatic involvement, have their serum PTH levels checked.