Source of this article: Chinese Journal of Oncology, 2021, 43(12): 1287-1291. Cited by this article: Zhai Jie, Kong Xiangyi, Fang Yi, et al. Clinical characteristics and prognosis of bipolar primary breast cancer and thyroid cancer [J]. Abstract Objective To explore the clinical

Source of this article: Chinese Journal of Oncology, 2021, 43(12): 1287-1291. Citation of this article: Zhai Jie, Kong Xiangyi, Fang Yi, et al. Clinical characteristics and prognosis of bipolar primary breast cancer and thyroid cancer [J].

Abstract

Targeted Targeted Targeted Targeted Targeted Targeted thyroid cancer patients. method retrospectively collected clinical pathological data of patients with bigenic primary cancer of breast cancer at the Cancer Hospital of the Chinese Academy of Medical Sciences from 2001 to 2020. The Kaplan-Meier method was used for survival analysis, and the Cox risk regression model was used for multi-factor analysis. Results The whole group of 98 patients were all female, the first tumor was confirmed to be 26-72 years old, and the median age was 47 years old. There were 18 cases in the group with breast cancer recurring thyroid cancer (breast tar) and 60 cases in the group with thyroid cancer recurring thyroid cancer (breast tar) and 20 cases in the group with breast cancer and thyroid cancer occur simultaneously (the diagnosis interval between the two is within 3 months, and at the same time). The differences in breast cancer pathological grading of breast cancer in patients with lactic dysty, breast dysty and concurrent groups were statistically significant, whether breast cancer was radiotherapy after surgery, and whether other tumors were combined (all P.05). Among the 98 patients in the whole group, 14 cases of recurrence and metastasis were 7 cases of death, and all patients with thyroid cancer were thyroid cancer and breast cancer. There was no significant difference in death and recurrence and metastasis in patients with the lactic anatomy group, the lactic anatomy group and the concurrent group (all P.05). Single-factor analysis showed that breast cancer stage and estrogen receptor (ER) were related to overall survival (all P.05), and family history of breast cancer, breast cancer stage, ER were related to recurrence-free metastasis (all P.05). Multivariate analysis showed that family history of breast cancer, ER positive, and tumor diagnosis sequence (breast cancer recurrence in thyroid cancer) were independent influencing factors without recurrence and metastasis (all P.05). Conclusion Breast cancer thyroid cancer patients with bipartite primary cancer, ER negative is an independent adverse factor in prognosis.

Multiple primary cancers refer to the occurrence of two or more primary malignant tumors in the same body at the same time or in succession. According to the time sequence of multiple tumors, it is divided into simultaneous multiple primary carcinoma and metachronous multiple primary carcinoma. In recent years, the number of patients with multiple primary cancers has gradually increased, among which breast cancer combined with thyroid cancer is more common and the incidence is gradually increasing. Studies have shown that when the first primary cancer is thyroid cancer, the most common secondary primary cancer is breast cancer; similarly, thyroid cancer is also the most common malignant tumor in breast cancer that occurs in the second tumor [1]. Previous single-center studies have reported that in patients with breast cancer, thyroid cancer, different tumor timings may have different mechanisms [2]. In order to further clarify the clinical pathological characteristics and prognosis of patients with bisectomy primary cancer and thyroid cancer, and compare the differences in pathological characteristics between different tumor sequences, in this study, we retrospectively analyzed the clinical pathological data of patients with bisectomy primary cancer and thyroid cancer at the Cancer Hospital of the Chinese Academy of Medical Sciences, and the report is now as follows.

Data and methods 1. Clinical data: selected 98 patients diagnosed with breast cancer and thyroid cancer or other primary cancers in our hospital from January 1, 2001 to December 31, 2020. According to the tumor occurrence time, the patients were divided into (1) thyroid cancer recurring thyroid cancer (breast tar) group; (2) thyroid cancer recurring thyroid cancer (breast tar) group; (3) breast cancer and thyroid cancer occur simultaneously (the diagnosis time interval between the two is within 3 months, and at the same time). All patients underwent radical thyroid cancer resection and radical breast cancer surgery. After the operation, whether to supplement 31I nuclide therapy or adjuvant chemotherapy, radiation therapy, endocrine therapy and targeted therapy are determined based on the pathological conditions.2. Baseline data collection and follow-up: (1) Collected baseline data of patients such as age, gender, marital status, maternity, menopause status, smoking, alcohol consumption, family history, diagnosis date, surgery date, treatment method, thyroid function, tumor stage (breast cancer stage and thyroid cancer stage are all staging system, pathological type, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and Ki-67 status, etc. Follow-up was carried out by telephone to collect the patient's recurrence, metastasis and survival information. The follow-up was as of January 31, 2021, with a follow-up of 8 to 352 months, with a median follow-up time of 108 months. Among the 98 patients in the whole group, 4 were lost to follow-up, with a loss of 4.1%. 3. Statistical analysis: was used for statistical analysis using SPSS 24.0 software. The comparison of the normal distribution of metrological data was performed by t test, the comparison of count data was performed by χ2 or Fisher's exact test, survival analysis was performed by Kaplan-Meier method (Log rank or Breslow test), and the Cox risk regression model was used for multi-factor analysis. All tests are two-sided tests, and the test level α=0.05.

Result

1. Clinical pathological characteristics:

The whole group of 98 patients were all female, 18 cases in the lactation group (18.4%), 60 cases in the lactation group (61.2%), and 20 cases in the same group (20.4%); the first tumor was confirmed at 26 to 72 years old, and the median age was 47 years old. There were 10 patients with bilateral breast cancer, and 14 patients with ≥3 primary malignant tumors, including 8 cases of lung cancer, 2 cases of ovarian cancer, 1 case of endometrial cancer, 1 case of colon cancer, 1 case of immature teratoma, 1 case of endodermal sinus tumor, 1 case of lymphoma, and 1 case of breast fibrosarcoma. Among the patients in the whole group, 6 cases had breast cancer susceptibility gene mutations. The interval between tumors in the lactate group is 4 to 255 months, and the median interval is 36.5 months; the interval between tumors in the lactate group is 4 to 338 months, and the median interval is 41.5 months. The clinical pathological characteristics of the patients in the whole group are shown in Table 1.

lactation staging, breast cancer pathological grading, whether breast cancer was radiotherapy after surgery, and whether other tumors were combined were statistically significant (all P.05, Table 1). There were more patients in the malignant group than in the malignant group and the simultaneous group (both P.05), and there was no significant difference between the malignant group and the simultaneous group (P.05). The Bonferroni method was used to adjust the α level to 0.016 7. The difference in postoperative radiotherapy of breast cancer between the lactation group and the concurrent group was statistically significant (P=0.007). The difference in postoperative radiotherapy of breast cancer between the lactation group and the concurrent group was statistically significant (P.001), but there was no statistically significant difference between the lactation group and the lactation group (P=0.284).

2. Prognosis analysis: Among the 98 patients in the whole group, 14 cases of recurrence and metastasis, 2 of which were thyroid cancer recurrence and metastasis, and 12 cases were breast cancer recurrence and metastasis; 7 cases died, including 2 deaths due to breast cancer metastasis, 2 deaths due to thyroid cancer metastasis, 1 death with primary lung cancer metastasis, and 2 deaths due to non-tumor causes. All patients who die due to tumors are thyroid cancer and breast cancer. There was no significant difference in death and recurrence and metastasis in patients with the lactic anatomy group, the lactic anatomy group and the concurrent group (all P.05).

3. Analysis of influencing factors: single-factor analysis showed that breast cancer stage and ER were related to overall survival (all P.05), breast cancer family history, breast cancer stage, ER and recurrence-free metastasis (all P.05), breast cancer family history, ER and PR status were related to thyroid cancer-specific recurrence-free metastasis (all P.05), and breast cancer stage was related to breast cancer-specific recurrence-free metastasis (P.001, Table 2).

Cox multi-factor analysis showed that the family history of breast cancer, ER positive, and tumor diagnosis sequence were independent influencing factors without recurrence and metastasis (all P0.05). Patients with a family history of breast cancer have a higher risk of recurrence and metastasis (HR = 13.793, 95% CI is 2.899~65.614, P = 0.001); compared with ER-negative patients, ER-positive patients have a lower risk of recurrence and metastasis (HR = 0.121, 95% CI is 0.029~0.505, P = 0.004); from the order of tumor diagnosis, compared with the simultaneous group, the risk of recurrence and metastasis in patients with breast aphrodisiac group was lower (HR = 0.107, 95% CI is 0.203~0.506, P = 0.005), and there is no statistically significant difference between the simultaneous group and the simultaneous group (P = 0.107, Table 3). Cox multi-factor analysis of breast cancer-specific recurrence and metastasis showed that the family history of breast cancer, ER, and tumor diagnosis sequence are independent influencing factors affecting breast cancer recurrence and metastasis in patients with binuclear primary cancer (all P0.05). Patients with a family history of breast cancer have a higher risk of recurrence and metastasis (HR = 9.017, 95% CI is 1.742~46.680, P = 0.009); compared with ER-negative patients, ER-positive patients have a lower risk of recurrence and metastasis (P = 0.030); from the order of tumor diagnosis, compared with the same group, patients in breast aphrodisiac group have a lower risk of recurrence and metastasis (HR = 0.095, 95% CI is 0.019~0.467, P=0.004, Table 4).

Discussion In recent years, the incidence of breast cancer has increased rapidly. In 2020, breast cancer surpassed lung cancer and became the highest incidence malignant tumor in my country and the world [3]. Among patients with multiple primary cancers, breast cancer combined with thyroid cancer is the most common [4,5]. Both the thyroid and breast are related to hormones, and changes in the endocrine system are closely related to the occurrence of thyroid tumors and breast tumors. Some studies have shown that the family history of breast cancer, ER status, PR status, thyroid hormone 3, etc. are related to the occurrence of thyroid and breast tumors [6,7,8], but there are few reports on related studies and the sample size is small. Large sample studies are limited to the exploration and analysis of the US surveillance, epidemiology and final results databases. The clinical and pathological data obtained are limited, and there are few reports on breast and thyroid cancer of different sequences. Zhang et al. [9] compared the analysis of 91 patients with breast cancer recurring thyroid cancer and 117 patients with thyroid cancer recurring breast cancer. The results showed that the interval between the two tumor diagnosis periods was shorter than the group with thyroid cancer recurring breast cancer recurring breast cancer, which was consistent with the results of this paper. Among the 98 patients in this study, 81 were ER-positive, which was consistent with previous studies. ER-positiveness was related to survival and recurrence and metastasis, and was also an independent influencing factor of recurrence and metastasis. This may be related to the metabolic mode of ER in patients with binuclear cancer [10,11]. Studies have shown that among patients with breast cancer recurring thyroid cancer, ER has significant differences in expression in breast cancer and thyroid cancer, and there is no significant difference in expression in patients with breast cancer recurring thyroid cancer and single-epidemic thyroid cancer [12]. The expression of ER and PR in breast cancer patients with thyroid cancer is higher than that of [8] in single-brother cancer patients, indicating that ER may be closely related to the incidence of thyroid cancer. The mechanism of action of ER in breast cancer is relatively mature, but the role of ER in the pathogenesis of thyroid cancer is relatively rare. Studies have shown that estrogen can promote the proliferation of thyroid cancer cells. At the same time, with the increase in Bcl-2 protein levels and the decrease in Bax protein levels in ERK1/2-related pathways, knocking out ERα can attenuate the expression of Bcl-2 and pERK1/2 mediated by estrogen 2 (E2), while knocking out ERβ can enhance the expression of Bcl-2 and pERK1/2 mediated by E2 [11]. Therefore, the imbalance between ERα and ERβ may be one of the causes of thyroid carcinoma. The role and specific mechanism of ER in breast cancer and thyroid cancer are still unclear. Previous studies on breast cancer with different sequences of thyroid cancer show that simultaneous bipolar primary carcinoma has a worse prognosis than metachronous bipolar primary carcinoma, and simultaneous bipolar primary carcinoma is an independent influencing factor of recurrence-free survival [2]. This study showed that compared with patients in the concurrent group, patients with the malaria group had a lower risk of recurrence and metastasis, and the malaria group was also an independent influencing factor in recurrence-free survival. This difference may be related to the sample size difference in the study. This study has limitations. First, the sample size in this study is smaller than that of large-scale foreign databases, and some patients have missing information, because there are fewer patients with double primary thyroid cancer than patients with single tumors. In this study, we counted all patients with binuclear primary cancers of any tumor confirmed by our hospital from 2001 to 2020. Some patients were diagnosed with the first tumor earlier and failed to obtain relevant clinical data. However, compared with reports from other domestic centers, the number of cases in this study is large, and this result shows that more patients in the lactate group had combined with the third primary carcinoma, and there were no relevant reports in previous studies. Secondly, because the tumor occurrence timing cannot be determined, the tumor sequence in this study is the two tumor diagnosis sequences, which may not be consistent with the occurrence timing. This study only conducted a retrospective analysis of clinical and pathological data. In the future, based on the results of this study, multi-center prospective research can be conducted in conjunction with other medical center data, and more cases can be included to study breast cancer tissue and thyroid cancer tissue from a molecular epigenetic perspective to explore their mechanisms and rules, and provide more treatment options for patients with binuclear primary cancer. For single breast cancer (especially ER-positive single breast cancer patients) or single thyroid cancer patients, the thyroid or breast gland should be checked regularly during the follow-up examination. In addition, patients with binuclear primary cancers of breast cancer and thyroid cancer should focus on systemic examinations during the follow-up examination and beware of the emergence of third primary malignant tumors. To sum up, the family history of breast cancer, ER positive, and tumor diagnosis sequence are independent influencing factors in the recurrence and metastasis of bisectomy primary cancers in breast cancer. ER positive plays an important role in the occurrence and prognosis of bisectomy primary cancers, but its specific mechanism still needs further research.