Subcutaneous implantation of thyroid carcinoma and benign tissue after thyroidectomy: report on two cases and review of the current literature.

Background: Subcutaneous implantation of thyroid tissue after thyroidectomy is a rare occurrence involving both benign and malignant thyroid tissue. Clinically, subcutaneous implantation of thyroid tissue can be challenging to diagnose. We present two cases of subcutaneous implantation of thyroid tissue following thyroidectomy and discuss the differential diagnosis, clinicopathological characteristics, and the possible mechanism of implantation. Case Description: A 35-year-old woman (age in 2009) who underwent total thyroidectomy in 2009 whose histopathological examination revealed a nodular hyperplasia and lymphocytic thyroiditis complained of palpable mass in her neck 10 years after operation and underwent excision. Follicular adenoma was confirmed in histopathological results. A 58-year-old woman (age in 2010) who underwent lobectomy in 2010 for nodular hyperplasia had a 6 cm sized huge mass in her anterior neck 9 years after operation. Anterior neck mass excision was done and poorly differentiated carcinoma was confirmed in histopathological results. The patient showed no sign of recurrence after 3 years follow-up. Conclusions: Subcutaneous implantation of benign thyroid tissue or thyroid cancer can occur after thyroidectomy. Minimizing the likelihood of subcutaneous implantation requires careful consideration of various factors at every stage of the surgical procedure. Surgeons should be aware of this potential long-term complication that can occur in both conventional thyroidectomy and remote access surgery, effectively communicate and provide appropriate guidance to their patients, and try to avoid seeding of both malignant and benign thyroid tissue.

CD39+ tissue-resident memory CD8+ T cells with a clonal overlap across compartments mediate antitumor immunity in breast cancer.

Despite being a standard treatment option in breast cancer, immune checkpoint inhibitors (ICIs) are only efficacious for a subset of patients. To gain a better understanding of the antitumor immune response in breast cancer, we examined the heterogeneity of CD8+ T cells in tumors, metastatic lymph nodes (mLNs), and peripheral blood from patients with early breast cancer (n = 131). Among tissue-resident memory CD8+ T (TRM) cells, including virus- and tumor-specific CD8+ T cells, CD39 expression was observed in a tumor-specific and exhausted subpopulation in both tumors and mLNs. CD39+ TRM cells from tumors and mLNs exhibited a phenotypic similarity and clonally overlapped with each other. Moreover, tumor or mLN CD39+ TRM cells clonally overlapped with CD39- TRM and non-TRM cells in the same compartment, implying a tissue-specific differentiation process. These inter-subpopulationally overlapping CD39+ TRM clonotypes were frequently detected among effector memory CD8+ T cells in peripheral blood, suggesting a systemic clonal overlap. CD39+ TRM cell enrichment was heterogeneous among molecular subtypes of breast cancer, which is associated with the different role of antitumor immune responses in each subtype. In vitro blockade of PD-1 and/or CTLA-4 effectively restored proliferation of CD39+ TRM cells and enhanced cytokine production by CD8+ T cells from tumors or mLNs, particularly in the presence of CD39+ TRM enrichment. This suggests that CD39+ TRM cells have a capacity for functional restoration upon ICI treatment. Thus, our study indicates that CD39+ TRM cells with a clonal overlap across compartments are key players in antitumor immunity in breast cancer.

Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer.

We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies' nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP, and EREG, and two genes were downregulated, including CXCL9 and GNLY. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer.

The Radiological Response Rate Pattern Is Associated With Recurrence Free Survival in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

PURPOSE: The aim of this study was to evaluate the radiological response rate patterns during neoadjuvant chemotherapy (NAC) in patients with breast cancer. METHODS: Patients who underwent NAC with two specific chemotherapy regimens (doxorubicin with cyclophosphamide or doxorubicin with docetaxel) and who underwent a response evaluation every two cycles were included in the study. The initial response ratio was defined as the ratio of the largest tumor diameter at diagnosis to that after two cycles of NAC. The latter response ratio was defined as the ratio between the tumor size after two cycles and that after four cycles of NAC. The radiological response rate pattern was divided into three groups: the fast-to-slow response group (F-S group, initial response ratio > latter response ratio + 20%), slow-to-fast response group (S-F group, latter response ratio > initial response ratio + 20%), and constant response group (less than 20% difference between the initial and latter response ratios). RESULTS: In total, 177 patients were included in the analysis. Forty-two (23.9%) patients were categorized into the F-S group, 26 (14.8%) into the S-F group, and 108 (61.2%) into the constant group. Clinicopathologic factors did not differ according to radiologic response rate patterns. The median follow-up period was 50 months (range, 3-112) months. In the univariate analysis, the F-S group had a significantly worse recurrence-free survival than the S-F and constant groups (hazard ratio [HR], 3.63; 95% confidence interval [CI], 1.05-12.46; p = 0.041). The F-S group also presented with significantly worse survival than the S-F group in the multivariate analysis (HR, 3.45; 95% CI, 1.00-11.89; p = 0.049). CONCLUSION: The F-S group had a poorer survival rate than the S-F group. Radiological response rate patterns may be useful for accurate prognostic assessments, especially when considering post-neoadjuvant therapy.

Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society.

BACKGROUND: There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody-drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. METHODS: Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan-Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. RESULTS: HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49-0.93; P = 0.019). CONCLUSIONS: These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.

PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Axillary lymph node dissection is not obligatory in breast cancer patients with biopsy-proven axillary lymph node metastasis.

PURPOSE: The ACOSOG Z0011 trial demonstrated that axillary lymph node dissection (ALND) is unnecessary in select patients with cT1-2N0 tumors undergoing breast-conserving therapy with 1-2 positive sentinel lymph nodes (SLNs). However, patients with preoperatively confirmed ALN metastasis were not included and may be subjected to unnecessary ALND. The aim of this study is to identify patients who can be considered for ALND omission when the preoperative ALN biopsy results are positive. METHODS: Breast cancer patients who underwent preoperative ALN biopsy and primary surgery were retrospectively reviewed. Among patients with positive ALN biopsy results, clinicopathological and imaging characteristics were compared according to LN disease burden (1-2 positive LNs vs. ≥ 3 positive LNs). RESULTS: A total of 542 patients were included in the analysis. Among them, 225 (41.5%) patients had a preoperative positive ALN biopsy. More than 40% of the patients (n = 99, 44.0%) with a positive biopsy had only 1-2 positive ALNs. The association between nodal burden and imaging factors was strongest when ≥ 2 suspicious LNs were identified on PET/CT images (HR 8.795, 95% CI 4.756 to 13.262). More than one imaging modality showing ≥ 2 suspicious LNs was also strongly correlated with ≥ 3 positive ALNs (HR 5.148, 95% CI 2.881 to 9.200). CONCLUSIONS: Nearly half of patients with a preoperative biopsy-proven ALN metastasis had only 1-2 positive LNs on ALND. Patients meeting ACOSOG Z0011 criteria with only one suspicious LN on PET/CT or those presenting with few abnormal ALNs on only one imaging modality appear appropriate for SLNB and consideration of ALND omission.

Hormone Replacement Therapy, Breast Cancer Risk Factors, and Breast Cancer Risk: A Nationwide Population-Based Cohort.

BACKGROUND: Hormone replacement therapy (HRT) increases the risk of breast cancer, but the association may vary according to patient factors. We investigated the association between HRT and breast cancer in a nationwide cohort with risk stratification according to risk factors for breast cancer. METHODS: Using the Korean National Health Insurance Service database, 4,558,376 postmenopausal women who underwent breast cancer screening and regular health checkups from 2009 to 2014 were analyzed. RESULTS: A total of 696,084 (15.3%) women reported current or previous HRT use. Breast cancer was newly diagnosed in 26,797 (0.6%) women during a median follow-up of 5.35 years. The HR of the risk of breast cancer in HRT users was 1.25 [95% confidence interval (CI), 1.22-1.29] compared with HRT nonusers. The risk of breast cancer increased according to HRT duration [adjusted HR = 1.08; 95% CI, 1.04-1.12, for <2 years; adjusted HR = 1.33; 95% CI, 1.25-1.40, for 2 to <5 years; and adjusted HR = 1.72; 95% CI, 1.63-1.82, for ≥5 years). The effects of HRT on breast cancer risk applied to both invasive and in situ cancer. The HRT-related risk of breast cancer was higher in women who were leaner and those who had dense breasts. CONCLUSIONS: This nationwide population-based study confirms the association between HRT use and breast cancer risk. The risk increased proportionally with duration of HRT and differed according to body weight and breast density. IMPACTS: Risk stratification would be useful when deciding whether to apply HRT for relief of menopausal symptoms.