Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response

유재민,이현준,한원식,이한별,안성귀,김희정,박형석,최지수,김해영,조원경,이정언 한국유방암학회 2024 Journal of breast cancer Vol.27 No.2

Purpose The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. Methods ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1–3N0–1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. Discussion Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. Trial Registration ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021. Purpose The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. Methods ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1–3N0–1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. Discussion Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. Trial Registration ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Biologic subtype is a more important prognostic factor than nodal involvement in patients with stages I and II breast carcinoma

Hyosun Kim,Jihyoung Cho,Sun Young Kwon,Sun Hee Kang 대한외과학회 2015 Annals of Surgical Treatment and Research(ASRT) Vol.90 No.1

Purpose: Nodal infiltration has been one of the most important prognostic factors in breast cancer. In recent decades, risk stratification has greatly changed, and is applied in accordance with hormone receptor and human epidermal growth factor receptor 2 (HER2) status. We compared the prognostic power of tumor subtype to nodal involvement in early breast cancer. Methods: We reviewed the medical records of 505 patients who had curative surgery for stage I or II breast cancer. We analyzed clinicopathologic factors according to tumor subtype and nodal involvement. Tumors were classified into 4 subtypes according to immunohistochemical status of estrogen receptor, progesterone receptor, HER2, and Ki67 labeling index. Disease-free survival (DFS) and overall survival were analyzed. Results: There were 363 node-negative patients (71.9%) and 142 node-positive patients (28.1%). Luminal A, Luminal B, HER2, and triple-negative breast cancer subtypes were composed of 207 (41.0%), 147 (29.1%), 42 (8.3%), and 109 patients (21.6%), respectively. The median follow-up period was 89.5 months. Node negative-luminal A subtype showed the best prognosis with regard to 5-year DFS, and the pN1-triple negative subtype was associated with the shortest DFS (95.1% vs. 67.8%; hazard ratio, 9.554; P < 0.001). However, the node negative-triple negative subtype was associated with a worse 5-year DFS than the pN1-luminal A subtype ([86.4%; hazard ratio, 2.647; P = 0.048] vs. [93.2%; hazard ratio, 2.061; P = 0.194]). Conclusion: Node negative-triple negative breast cancer was associated with a poorer prognosis than pN1-luminal A subtype. Tumor subtype has greater prognostic power compared to nodal status in early breast cancer.

Breast Cancer Recurrence According to Molecular Subtype

Shim, Hee Jin,Kim, Sung Hun,Kang, Bong Joo,Choi, Byung Gil,Kim, Hyeon Sook,Cha, Eun Suk,Song, Byung Joo Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: To evaluate the location of tumor relapse and imaging modality for detection according to the breast cancer subtype: luminal A, luminal B, HER2 positive luminal B, nonluminal HER2 positive, and triple negative. Materials and Methods: A total of 1244 patients with breast cancer with known estrogen receptor (ER), progesterone receptor (PR), Ki-67 and human epidermal growth factor receptor 2 (HER2), who underwent breast surgery from 2009 to 2012 were analyzed. Patients were classified into the following categories: luminal A (n=458), luminal B (n=241), HER2 positive luminal B (n=227), nonluminal HER2 positive (n=145) and triple negative (n=173). A total of 105 cases of relapse were detected in 102 patients: locoregional recurrence (n=46), recurrence in the contralateral breast (n=28) and distant metastasis (n=31). Comparison of proportions was used to determine the difference between subtypes. Results: Relapse rates by subtypes are as follows: luminal A 23 of 458 (5.02%), luminal B 19 of 241(7.88%), HER2 positive luminal B 15 of 227 (6.61%), nonluminal HER2 postive 19 of 145 (13.10%) and triple negative 29 of 173(16.76%). Luminal A tumors had the lowest rate of recurrence and had significantly lower recurrence rate in comparison with nonluminal HER2 postive (p=0.0017) and triple negative subtypes (p<0.0001). Compared with all other subtypes except nonluminal HER2 positive, triple negative tumors had the highest rate of tumor recurrence (p<0.01). Triple negatives were most likely to develop contralateral recurrence against all subtypes (p<0.05). Detection rate of locoregional and contralateral tumor recurrence were 28.3% on mammography (n=17/60). Conclusions: Luminal A tumors are associated with a low risk of recurrence while triple negative lesions have a high risk. In case of triple negative tumors, the contralateral breast has much more recurrence as compared with all other subtype. In terms of detection rates, breast USG was the best modality for detecting tumor recurrence, compared with other modalities (p<0.05). Subtyping of breast tumors using a molecular gene expression panel can identify patients who have increased risk of recurrence and allow prediction of locations of tumor recurrence for each subtype.

호르몬 수용체 약양성 유방암과 삼중음성 유방암의 치료 예후

윤미란,류지영,송병주,채병주,유태경 한국유방암학회 2019 Journal of Breast Disease Vol.7 No.1

Purpose: In breast cancer, response to endocrine therapy depends on estrogen receptor and progesterone receptor status. However, poor prognosis is conferred on patients with hormone receptor (HR)-positive breast cancer. We aimed to examine weakly positive HR breast cancer by comparing weakly positive HR to strongly positive HR and negative HR breast cancer. Methods: We examined the clinical and biological features of 1,496 women with breast cancer, and these patients were categorized according to HR status as weakly positive, strongly positive, and negative HR breast cancer. Results: In this study, among 1,496 patients with breast cancer, negative HR breast cancer was found in 374, weakly positive HR breast cancer in 90 and strongly positive HR breast cancer in 1,032 patients. Our multivariate analysis showed that there were differences in T stage, tumor–node–metastasis stage, vascular invasion, histologic grade and type, and Ki-67 index. Patients with weakly positive HR breast cancer had an increased risk of death and recurrence compared with those with strongly positive HR breast cancer and had similar prognosis as patients with negative HR breast cancer. Conclusion: Patients with weakly positive HR breast cancer received endocrine therapy because they were regarded as having positive HR breast cancer. However, their prognosis of overall survival and relapse-free survival was similar to that in patients with negative HR breast cancer. Therefore, we need to closely observe and consider active treatment for patients with weakly positive breast cancer.

Very Rare Case of Spindle Cell Carcinoma of Breast in Male

조세나,김유석,김권천 한국유방암학회 2014 Journal of Breast Disease Vol.2 No.2

Metaplastic breast carcinoma is uncommon, constitutes ≤5% of all breast cancers, and is classified into various subtypes with varying incidences. Of these subtypes, spindle cell carcinoma represents approximately 0.3% of all invasive breast carcinomas in women. The spindle cell carcinoma subtype of metaplastic breast carcinoma is typically triple negative and has distinct clinical, radiological, and pathological characteristics. To date, there is no effective treatment for this malignancy. Herein, we report a case of spindle cell carcinoma of the breast in a 71 year-old man who presented with a palpable mass in his left breast. Breast ultrasonography revealed a 1.1×2.6 cm hypoechoic well-demarcated ovoid mass. The patient underwent excisional biopsy. Pathological findings indicated a diagnosis of spindle cell carcinoma of the breast, and the patient underwent a modified radical mastectomy. The final pathological report indicated a 6.5×3.0 cm malignant spindle cell tumor.

The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge

Daiana Cosmina Temian,Laura Ancuta Pop,Alexandra Iulia Irimie,Ioana Berindan-Neagoe 한국유방암학회 2018 Journal of breast cancer Vol.21 No.3

Breast cancer has the highest incidence among all malignancies diagnosed in women. Therapies have significantly improved over the years due to extensive molecular and clinical research; in a large number of cases, targeted therapies have provided better prognosis. However, one specific subtype remains elusive to targeted therapies—the triple-negative breast cancer. This immunohistochemically defined subtype is resistant to both endocrine and targeted therapies, leading to its poor prognosis. A field that is of great promise in current cancer research is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis— DNA methylation, histone modifications, and noncoding RNAs— advances in cancer treatment, diagnosis, and prevention are possible. This review aims to synthesize the epigenetic discoveries that have been made related to the triple-negative breast cancer.

Breast Conservation Therapy versus Mastectomy in Patients with T1-2N1 Triple-Negative Breast Cancer: Pooled Analysis of KROG 14-18 and 14-23

김규보,박혜진,신경환,김진호,최두호,박원,안승도,김수산,김대용,김태현,김진희,김지영 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The aim of this study is to compare the treatment outcomes of breast conserving surgery (BCS) plus radiotherapy (RT) versus mastectomy for patients with pT1-2N1 triple-negative breast cancer (TNBC). Materials and Methods Using two multicenter retrospective studies on breast cancer, a pooled analysis was performed among 320 patients with pT1-2N1 TNBC. All patients who underwent BCS (n=212) received whole breast RT with or without regional nodal RT, while none who underwent mastectomy (n=108) received it. All patients received taxane-based adjuvant chemotherapy. The median follow-up periods were 65 months in the BCS+RT group, and 74 months in the mastectomy group. Results The median age of all patients was 48 years (range, 24 to 70 years). Mastectomy group had more patients with multiple tumors (p < 0.001), no lymphovascular invasion (p=0.001), higher number of involved lymph node (p=0.028), and higher nodal ratio  0.2 (p=0.037). Other characteristics were not significantly different between the two groups. The 5-year locoregional recurrence-free, disease-free, and overall survival rates of BCS+RT group versus mastectomy group were 94.6% versus 87.7%, 89.5% versus 80.4%, and 95.0% versus 87.8%, respectively, and the differences were statistically significant after adjusting for covariates (p=0.010, p=0.006, and p=0.005, respectively). Conclusion In pT1-2N1 TNBC, breast conservation therapy achieved better locoregional recurrencefree, disease-free, and overall survival rates compared with mastectomy.

Use of positron emission tomography-computed tomography to predict axillary metastasis in patients with triple-negative breast cancer

Jung Hyun Youm,Yoona Chung,You Jung Yang,한상아,송정윤 대한종양외과학회 2018 Korean Journal of Clinical Oncology Vol.14 No.2

Purpose: Axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) are important for staging of patients with node-posi�tive breast cancer. However, these can be avoided in select micrometastatic diseases, preventing postoperative complications. The present study evaluated the ability of axillary lymph node maximum standardized uptake value (SUVmax) on positron emission tomography-comput�ed tomography (PET-CT) to predict axillary metastasis of breast cancer. Methods: The records of invasive breast cancer patients who underwent pretreatment (surgery and/or chemotherapy) PET-CT between Janu�ary 2006 and December 2014 were reviewed. ALNs were preoperatively evaluated by PET-CT. Lymph nodes were dissected by SLNB or ALND. SUVmax was measured in both the axillary lymph node and primary tumor. Student t-test and chi-square test were used to analyze sensitivi�ty and specificity. Receiver operating characteristic (ROC) and area under the ROC curve (AUC) analyses were performed. Results: SUV-tumor (SUV-T) and SUV-lymph node (SUV-LN) were significantly higher in the triple-negative breast cancer (TNBC) group than in other groups (SUV-T: 5.99, P<0.01; SUV-LN: 1.29, P=0.014). The sensitivity (0.881) and accuracy (0.804) for initial ALN staging were high�er in fine needle aspiration+PET-CT than in other methods. For PET-CT alone, the subtype with the highest sensitivity (0.870) and negative predictive value (0.917) was TNBC. The AUC for SUV-LN was greatest in TNBC (0.797). Conclusion: The characteristics of SUV-T and SUV-LN differed according to immunohistochemistry subtype. Compared to other subtypes, the true positivity of axillary metastasis on PET-CT was highest in TNBC. These findings could help tailor management for therapeutic and diag�nostic purposes.

Overexpression of PRAT1 protein is closely related to triple-negative breast cancer

Sang Eun Nam,Young-Sin Ko,Kyoung Sik Park,TongYi Jin,Young-Bum Yoo,Jung-Hyun Yang,Wook-Youn Kim,Hye-Seung Han,So-Dug Lim,Seung Eun Lee,Wan-Seop Kim 대한외과학회 2022 Annals of Surgical Treatment and Research(ASRT) Vol.103 No.2

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of PRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of PRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of was assessed. Then, the expression of the PRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between PRAT1 expression and clinicopathological parameters in breast cancer patients. Finally, we determined the relationship between PRAT1 overexpression and prognosis in patients. Results: The expression of PRAT1 in breast cancer tissues is significantly higher than in normal tissue. PRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features: T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion: PRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of PRAT1 in breast cancer and the therapeutic target for TNBC.

Norepinephrine/β2-Adrenergic Receptor Pathway Promotes the Cell Proliferation and Nerve Growth Factor Production in Triple-Negative Breast Cancer

Meihua Jin,Yan Wang,Tingting Zhou,Wenzhe Li,Qingping Wen 한국유방암학회 2023 Journal of breast cancer Vol.26 No.3

Purpose: Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC. Methods: The expression levels of the β2-adrenergic receptor (β2-AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2-AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2-AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis. Results: The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2-AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the co-culture assay, the sympathetic adrenergic NE/β2-AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth. Conclusion: These results suggest that NE/β2-AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.