| Background:In recent years,breast cancer has become a major health problem for women due to its high morbidity and mortality rates,which rank first among female malignancies worldwide.The role of estrogen and progesterone in the pathogenesis and development of breast cancer is well established,and targeted endocrine therapy has also become a very important adjuvant treatment for breast cancer.However,the correlation between prolactin(PRL)and breast cancer is still controversial.Objective:Our study aimed to clarify the proportion of hyperprolactinemia in patients with breast disease,especially breast cancer,and to determine the correlation between hyperprolactinemia and different clinicopathological parameters of breast cancer.And we aimed to investigate the etiology of hyperprolactinemia in patients with breast disease combined with hyperprolactinemia.Materials and methods:In this study,we collected 2764 female patients who were hospitalized in the Breast Surgery Department of Qilu Hospital of Shandong University between January 2019 and June 2022 and had their serum PRL levels measured in a fasting state before surgery,including 1243 patients with benign breast disease and 1521 patients with breast cancer.We collected 201 healthy female patients who had their serum PRL levels tested in fasting at our Health Checkup Center from January 2022 to September 2022.We collected 168 patients with breast disease combined with hyperprolactinemia who underwent magnetic pituitary MRI(magnetic resonance imaging)at our hospital from March 2016 to August 2022.In this study,serum PRL levels were measured using a kit provided by Roche.Normal serum PRL concentrations in women range from 102μIU/ml to 496μIU/ml.Serum PRL levels above 496μIU/ml were diagnosed as hyperprolactinemia.Results:1.In our group of 2764 patients,hyperprolactinemia was detected in a total of 785 patients.The proportion of hyperprolactinemia in the breast cancer group,benign disease group and healthy women group were 23.47%、32.74%and 10.45%,respectively.There were statistical differences between all groups(P<0.001).In total,357 patients with hyperprolactinemia were detected in 1521 breast cancer patients.The proportion of hyperprolactinemia in patients aged<35 years,36～50 years and≥51 years were 50.00%,33.33%and 10.67%,respectively(P<0.001).The proportion of hyperprolactinemia in premenopausal and postmenopausal patients were 34.27%and 7.32%,respectively(P<0.001).The proportion of hyperprolactinemia in patients with age at menarche ≤12 years,13～14 years and≥15 years were 33.68%,27.20%and 16.67%,respectively(P<0.001).The proportion of hyperprolactinemia in unmaternal and menstrual patients were 58.33%and 22.00%,respectively(P<0.001).The proportion of hyperprolactinemia in patients with Body Mass Index(BMI)<24kg/m2 and BMI≥24 kg/m2 were 28.74%and 18.51%,respectively(P<0.001).The proportion of hyperprolactinemia patients in ER+and ER-groups were 24.33%and 19.34%,respectively(P<0.001).The proportion of patients with hyperprolactinemia was not related to different age at menopause and the presence of a family history of breast cancer in breast cancer patients(P>0.05).The proportion of PR+and PR-breast cancer patients were 24.68%and 19.36%,respectively(P<0.001).The proportion of hyperprolactinemia did not differ significantly among breast cancer patients with different histological grade,molecular type,clinical stage,number of axillary lymph node metastases,tumor size stage,pathological typing,Her-2 status,Ki-67 expression levels,presence of intraventricular thrombus and presence of nerval invasion(P>0.05).2.The median PRL levels in breast cancer group,benign disease group and healthy women group were 317.10(219.40,480.80)μIU/ml,392.41(267.50,572.82)μIU/ml and 235.50(165.40,346.40)μIU/ml,respectively.There were statistical differences between all groups(P<0.001).The median PRL levels in patients with breast cancer aged ≤35 years,36～50 years and≥51 years were 495.55(315.15,680.85)μIU/ml,386.30(284.10,568.20)μIU/ml and 244.30(181.95,345.05)μIU/ml,respectively(P<0.001).The median PRL levels in premenopausal and postmenopausal patients with breast cancer were 396.50(280.85,565.40)μIU/ml and 238.30(177.33,323.98)μIU/ml,respectively(P<0.001).The median PRL levels in breast cancer patients with age at menarche ≤12 years,13～14 years and ≥15 years were 379.00(252.50,595.35)μIU/ml,328.40(231.83,511.28)μIU/ml and 290.00(208.05,414.03)μIU/ml,respectively(P<0.001).The median PRL levels in unmaternal and menstrual patients were 548.40(370.48,927.30)μIU/ml and 313.10(216.25,470.20)μIU/ml,respectively(P<0.001).The median PRL levels in breast cancer patients with BMI<24 kg/m2 and BMI≥24 kg/m2 were 352.00(240.95,534.30)μIU/ml and 295.50(208.05,430.33)μIU/ml,respectively(P<0.001).PRL levels were not related to different age at menopause and the presence of a family history of breast cancer in breast cancer patients(P>0.05).The median serum PRL levels in patients with ER+and ER-breast cancer were 323.90(222.30,489.00)μIU/ml and 295.60(214.73,425.70)μIU/ml,respectively(P<0.05).The median serum PRL levels in patients with PR+and PR-breast cancer were 325.40(224.50,493.83)μIU/ml and 297.10(213.50,429.30)μlU/ml,respectively(P<0.05).The median serum PRL levels did not differ significantly among patients with different histological grade,molecular typing,clinical stage,number of axillary lymph node metastases,tumor size stage,pathological type,Her-2 status,Ki-67 expression levels,presence or absence of intraventricular thrombus and nerval invasion(P>0.05).3.Among the 168 patients with breast disease combined with hyperprolactinemia who underwent pituitary MRI,pituitary microadenoma was found in 56 patients,empty pterygoid saddle in 13 patients,Rathke’s cyst in 10 patients,and other abnormalities(pituitary hyperplasia,pituitary stalk deviation,abnormal signals,etc.)in 12 patients.The proportion of pituitary abnormalities between patients with benign breast disease and breast cancer were not significantly different(P>0.05).Patients with abnormal pituitary MRI results had higher and statistically different serum PRL levels than those with normal pituitary MRI.PRL levels≥784.5μIU/ml suggested the presence of pituitary lesion in patients with breast disease combined with hyperprolactinemia.This value corresponded to a maximum sensitivity of 68.13%and a maximus specificity of 68.83%.The area under curve(AUC)was 0.680(95%confidence interval was 59.81%to 76.21%).Conclusions:1.The proportion of hyperprolactinemia and serum PRL levels are higher in patients with breast disease than in the healthy population.2.The proportion of hyperprolactinemia is higher in breast cancer patients than in the healthy population,and is higher in younger(≤35 years),premenopausal,early age of menarche(≤12 years)and lower BMI,ER+,PR+breast cancer patients.2.PRL levels were higher in breast cancer patients than in healthy population.Higher PRL levels were associated with younger(≤35 years),premenopausal,early age of menarche(≤12 years)and lower BMI,ER+,PR+breast cancers.3.Patients with breast disease combined with pituitary lesion have higher PRL levels than those with normal pituitary gland.Serum PRL levels≥784.5μIU/ml in patients with breast disease combined with hyperprolactinemia suggest the possible presence of pituitary lesion. |
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