Long Term Effects of a Social Capital-Based Exercise Adherence Intervention for Breast Cancer Survivors With Moderate Fatigue: A Randomized Controlled Trial.

OBJECTIVES: This study reports on the long-term effects of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), implemented using a randomized controlled trial design. The study investigated outcomes related to cancer-related fatigue (CRF), quality of life (QOL), physical activity, depression, anxiety, sleep quality, and social capital. METHODS: Participants who had moderate or greater CRF were randomly assigned to the intervention (n = 24), consisting of supervised and home-based exercise, or the control (n = 26), who received exercise leaflets. Generalized estimating equations models were fitted for the outcome variables. The assessment points were baseline (M1), immediately after completing the intervention at 12 weeks (M2), 1 month (M3), and 6 months post-intervention (M4). RESULTS: A significant reduction in the total CRF score was found for both groups. We observed a significant time by group effect at M2, indicating a reduction of behavioral/severity CRF scores and a higher increase of physical activity. Also, there was an increase in the QOL score of both groups at M2, M3, and M4, compared to M1. Both groups had reduced anxiety at M3 and M4 compared to M1. The time by group effect for depression, sleep quality and social capital was not statistically significant. CONCLUSION: This 12-week exercise adherence program improved behavioral/severity CRF and physical activity post-intervention. Both the experimental group and control group showed significant improvements in CRF, QOL, and anxiety domains compared to the baseline, which extended to 6 months post-intervention. TRIAL REGISTRATION: Korean Clinical Research Information Service (KCT0005763).

Giant mixed hemangioma of the breast: A case report with imaging findings.

Hemangioma of the breast is an uncommon tumor type that is usually small, superficially located, and impalpable. The majority of cases are cavernous hemangiomas. We describe a rare case of a large, palpable mixed hemangioma of the breast which was located in the parenchymal layer, studied with magnetic resonance imaging, mammography, and sonography. Magnetic resonance imaging findings of slow and persistent enhancement from the center to periphery are useful in characterizing benign breast hemangiomas, where even the lesion presents with a suspicious shape and margin on sonography.

On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated. METHODS: Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics. RESULTS: In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency. CONCLUSIONS: On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.

Development and effects of a post-traumatic growth program for patients with breast cancer.

PURPOSE: This study aimed to develop a post-traumatic growth (PTG) program, based on the PTG promotion resources suggested by Cahlhoun, Cann, and Tedeschi, and to apply it to breast cancer patients to determine its effect. METHODS: A non-equivalent control group pretest-posttest experimental design was used. In total, 74 participants were enrolled in this study, with 37 in the experimental group and 37 in the control group. The PTG program developed in this study consisted of writing and self-reflection for self-analysis, talking and sharing for self-disclosure, and participation in a self-help group for social support. The instruments used for this study were the Korean version of the Event Related Rumination Inventory, the Korean version of the Hospital Anxiety and Depression Scale, and the Korean version of the Post-traumatic Growth Inventory. The data were analyzed with the χ2test, t-test, Fisher's exact test and all analysis were conducted based on an intention-to-treat principle. RESULTS: The experimental group that underwent a PTG program had a lower emotional distress score than the control group (anxiety: t = -3.84, p = .001; depression: t = -3.22, p = .002). The experimental group had a lower intrusive rumination (t = -3.55, p = .001) and had higher deliberate rumination score than the control group (t = 2.10, p = .039). The experimental group had a higher PTG score than the control group (t = 2.34, p = .022). CONCLUSIONS: The PTG program developed in this study for breast cancer patients has the potential to contribute to the promotion of PTG in breast cancer patients.

Effects of a partnership-based, needs-tailored self-management support intervention for post-treatment breast cancer survivors: A randomized controlled trial.

OBJECTIVE: To examine the effectiveness of partnErship-based, needs-tailored self-Management support Program fOr Women with breast cancER (EMPOWER), a partnership-based, needs-tailored, self-management (SM) support intervention designed to empower post-treatment breast cancer survivors (BCSs) and ultimately improve their health outcomes. METHODS: This multi-center, two-armed, randomized controlled trial comprised 94 female BCSs who had completed primary cancer treatment in South Korea. Participants were randomly assigned (1:1) to the intervention group or the wait-list control group. The intervention group received a 7-week EMPOWER intervention via telephone counseling. The primary outcome was empowerment. Secondary outcomes included self-efficacy for post-treatment SM behaviors, mental adjustment, anxiety, depression, and health-related quality of life. Data were collected via a self-reported questionnaire at baseline (T0) and at 8 (T1) and 20 weeks (T2) of follow-up. Linear mixed models were used to assess group differences over time. Effective sizes were calculated using Cohen's d. RESULTS: Retention rates were excellent (95.7% at T1; 94.7% at T2). Linear mixed model analyses revealed that the EMPOWER group showed significantly improved empowerment (mean difference 2.24, 95% CI = 0.18 to 4.29; p = 0.016) and general health perception (mean difference 3.68, 95% CI = 0.67 to 6.72; p = 0.037) compared with the control group. Time point analysis showed that several secondary outcomes significantly improved at T1, but the effects were not sustained. CONCLUSION: EMPOWER was effective in improving empowerment and general health perception among post-treatment BCS. Further studies are needed to determine the effectiveness of the EMPOWER intervention in other cancer populations.

Genomic landscape of extraordinary responses in metastatic breast cancer.

Extreme responders to anticancer therapy are rare among advanced breast cancer patients. Researchers, however, have yet to investigate treatment responses therein on the whole exome level. We performed whole exome analysis to characterize the genomic landscape of extreme responders among metastatic breast cancer patients. Clinical samples were obtained from breast cancer patients who showed exceptional responses to anti-HER2 therapy or hormonal therapy and from those who did not. Matched breast tumor tissue (somatic DNA) and blood samples (germline DNA) were collected from a total of 30 responders and 15 non-responders. Whole exome sequencing using Illumina HiSeq2500 was performed for all 45 patients (90 samples). Somatic single nucleotide variants (SNVs), indels, and copy number variants (CNVs) were identified for the genomes of each patient. Group-specific somatic variants and mutational burden were statistically analyzed. Sequencing of cancer exomes for all patients revealed 1839 somatic SNVs (1661 missense, 120 nonsense, 43 splice-site, 15 start/stop-lost) and 368 insertions/deletions (273 frameshift, 95 in-frame), with a median of 0.7 mutations per megabase (range, 0.08 to 4.2 mutations per megabase). Responders harbored a significantly lower nonsynonymous mutational burden (median, 26 vs. 59, P = 0.02) and fewer CNVs (median 13.6 vs. 97.7, P = 0.05) than non-responders. Multivariate analyses of factors influencing progression-free survival showed that a high mutational burden and visceral metastases were significantly related with disease progression. Extreme responders to treatment for metastatic breast cancer are characterized by fewer nonsynonymous mutations and CNVs.

Survival Rates of Breast Cancer Patients Aged 40 to 49 Years according to Detection Modality in Korea: Screening Ultrasound versus Mammography.

OBJECTIVE: The aim of this study was to compare the survival rates of Korean females aged 40 to 49 years with breast cancer detected by supplemental screening ultrasound (US) or screening mammography alone. MATERIALS AND METHODS: This single-institution retrospective study included 240 patients with breast cancer (mean age, 45.1 ± 2.8 years) detected by US or mammography who had undergone breast surgery between 2003 and 2008. Medical records were reviewed for clinicopathologic characteristics and detection methods. Disease-free survival (DFS) and overall survival (OS) were compared between patients with breast cancer in the US and mammography groups using the log-rank test. Multivariable cox regression analysis was used to identify independent variables associated with DFS and OS. RESULTS: Among the 240 cases of breast cancer, 43 were detected by supplemental screening US and 197 by screening mammography (mean follow-up: 7.4 years, 93.3% with dense breasts). There were 19 recurrences and 16 deaths, all occurring in the mammography group. While the US group did not differ from the mammography group in tumor stage, the patients in this group were more likely to undergo breast-conserving surgery and radiation therapy than the mammography group. The US group also showed better DFS (p = 0.016); however, OS did not differ between the two groups (p = 0.058). In the multivariable analysis, the US group showed a lower risk of recurrence (hazard ratio, 0.097; 95% confidence interval, 0.001-0.705) compared to the mammography group. CONCLUSION: Our study found that Korean females aged 40-49 years with US-detected breast cancer showed better DFS than those with mammography-detected breast cancer. However, there were no statistically significant differences in OS.

Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective.

OBJECTIVE: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making. SUMMARY BACKGROUND DATA: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear. METHODS: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients. RESULTS: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients). CONCLUSIONS: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk.

Conserving the lymphatics from the arm using fluorescence imaging in patients with breast cancer at high risk of postoperative lymphedema: a pilot study.

BACKGROUND: Postoperative lymphedema in breast cancer survivors is a serious complication that develops from axillary lymph node dissection (ALND), chemotherapy, and radiation therapy. Axillary reverse mapping (ARM) was recently introduced to reduce lymphedema. This pilot study aimed to investigate the feasibility of preserving the ARM node using fluorescence imaging for patients at high risk of lymphedema. METHODS: We prospectively screened patients with breast cancer who had pathologic node-positive disease at diagnosis and were scheduled for neoadjuvant chemotherapy (NCT). The sentinel lymph node (SLN) was identified using blue dye and radioisotope, while the ARM node was traced using indocyanine green (ICG). In cases in which SLN was negative on the intraoperative frozen section examination, the ARM node and lymphatics were preserved. RESULTS: Of the 20 screened patients, six whose metastatic axillary lymph node (ALN) was converted to clinically node-negative disease after NCT were enrolled. No patients experienced recurrence at 24 months postoperative. Four patients who had a preserved ARM node did not develop lymphedema. One patient whose ARM node was not preserved due to SLN identification failure did not develop postoperative lymphedema. One patient who underwent ALND without ARM node conservation because of metastatic SLN on frozen section examination developed postoperative lymphedema. CONCLUSIONS: ARM is oncologically safe, decreases the incidence of postoperative lymphedema, and allows for the early detection of postoperative lymphedema in patients who underwent ALND. Ultimately, ARM may help improve the quality of life of patients with pathologic node-positive breast cancer.

Correction to: Palbociclib use with grade 3 neutropenia in hormone receptor-positive metastatic breast cancer.

In the original publication of the article, under the Results section, subheading "Patient survival", the second sentence that reads as "The 6-month PFS was 92.4%, 81.8%, and 93.3% and the one-year PFS was 72.0%, 88.9%, and 78.9% in Groups 1-3, respectively." should read as "The 6-month PFS was 82.8%, 75.0%, and 68.0% and the one-year PFS was 77.0%, 62.0%, and 63.8% in Groups 1-3, respectively.".

Palbociclib use with grade 3 neutropenia in hormone receptor-positive metastatic breast cancer.

PURPOSE: Neutropenia is the most common toxicity of CDK4/6 inhibitors, causing frequent dose interruptions. However, CDK4/6 inhibitor-induced neutropenia shows a benign clinical course in contrast to that caused by chemotherapy. Here, we investigated the safety of a new dose scheme for palbociclib, which avoids dose delays or reductions due to afebrile grade 3 neutropenia. METHODS: A consecutive cohort of ER( +)/HER2( -) advanced breast cancer patients who received palbociclib between 2017 and 2018 was analyzed. The patients were classified into Group 1 (patients who maintained palbociclib dose with afebrile grade 3 neutropenia), Group 2 (patients who experienced any dose modification with afebrile grade 3 neutropenia), and Group 3 (patients without afebrile grade 3 neutropenia). The primary endpoint was febrile neutropenia incidence; other toxicities were compared with those of the PALOMA-2 trial. RESULTS: Among the 107 patients, 54.2%, 22.4%, and 23.4% were classified into Groups 1, 2, and 3, respectively. There was no febrile neutropenia in Groups 1 and 2 during palbociclib treatment. Group 1 showed higher incidence of thrombocytopenia (all-grade, 32.8%; grade 3-4, 8.6%) than Group 2 and the PALOMA-2 data, but there was no bleeding related to thrombocytopenia. Group 1 showed higher incidence of all-grade non-hematologic adverse events than Group 2; only one grade 3 non-hematologic toxicity was observed in Group 1. There were no treatment-related hospitalizations or deaths in Group 1. CONCLUSIONS: Thus, omitting palbociclib dose modification with afebrile grade 3 neutropenia is safe and tolerable without febrile neutropenia events. This scheme could be useful to avoid unnecessary reductions in palbociclib doses in future practice.

Author Correction: Robot-assisted Nipple-sparing Mastectomy with Immediate Breast Reconstruction: An Initial Experience.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Design of a randomized controlled trial of a partnership-based, needs-tailored self-management support intervention for post-treatment breast cancer survivors.

BACKGROUND: Self-management is becoming essential for breast cancer survivors, but evidence about the effectiveness of self-management support (SMS) intervention is lacking. To address this issue, we developed a theory-based SMS intervention, the 'EMPOWER', aimed at empowering breast cancer survivors. Here we describe the rationale of the intervention and its development. METHODS: The conceptual framework of this study is the Chronic Care Model, which posits that SMS can influence patient-provider relationships and ultimately improve health outcomes. We will conduct a multi-center, 2-armed randomized controlled trial to assess the effectiveness of EMPOWER among post-treatment breast cancer survivors in South Korea. The trial will include 94 women who completed primary breast cancer treatment within the last 6 months. Participants will be randomly assigned to the intervention group or the wait-list control group (1:1). The intervention group will receive a 7-week partnership-based and needs-tailored SMS intervention via telephone counseling. The primary outcome is empowerment. The secondary outcomes include self-efficacy for post-treatment self-management behaviors, mental adjustment, psychological distress, and health-related quality of life (HRQOL). Data will be collected by self-reported questionnaire at baseline, post-intervention, and 3-month follow-up. DISCUSSION: We believe that the EMPOWER intervention could improve HRQOL of post-treatment breast cancer survivors by enhancing their empowerment. If found successful, it could aid clinicians engaged in the long-term care of breast cancer survivors. TRIAL REGISTRATION: Clinical Research Information Service, KCT0004794. Registered 5 March 2020.

First Experience in Korea of Stereotactic Partial Breast Irradiation for Low-Risk Early-Stage Breast Cancer.

Purpose: Accelerated partial breast irradiation (A-PBI) in Korean women has been considered impracticable, owing to small breast volume and lack of high-precision radiotherapy experience. We present the first experience of stereotactic-PBI (S-PBI) with CyberKnife M6 to investigate feasibility of use and early toxicities in Korean women with early breast cancers. Materials and Methods: A total of 104 breasts receiving S-PBI at our institution between September 2017 and October 2018 were reviewed. Patients were selected based on the American Society for Radiation Oncology (ASTRO), American Brachytherapy Society, American Society of Breast Surgeons, and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology guidelines. A dose of 30 Gy in 5 fractions (NCT01162200) was used. Gold fiducials were routinely inserted near the tumor bed for tracking. Constraints regarding organs-at-risk followed the NSABP-B39/RTOG 0413 protocol. Results: Median follow-up was for 13 months. Patients were categorized as "suitable" (71.2%) or "cautionary" (28.8%) according to 2017 the ASTRO guidelines. No tracking failure of inserted gold fiducials occurred. Median planning target volume (PTV) and PTV-to-whole breast volume ratio was 73.6 mL (interquartile range, 58.8-103.9 mL) and 17.0% (13.3-19.1%), respectively. Median PTV V95%, PTV Dmax, and ipsilateral breast V50% were 97.8% (96.2-98.8%), 105.3% (104.2-106.4%), and 35.5% (28.3-39.8%), respectively. No immediate post-S-PBI toxicity ≥ grade 2 was reported, except grade 2 induration in three breasts. All patients remain disease-free to date. Conclusion: The first use of S-PBI in Korean women was feasible and safe for selected early breast cancer. Based on these results, we have initiated a prospective study (NCT03568981) to test S-PBI in whole-breast irradiation for low-risk early breast cancer.

Assessment of the Prognostic Staging System of American Joint Committee on Cancer 8th Edition for Breast Cancer: Comparisons with the Conventional Anatomic Staging System.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual introduced a new prognostic staging system for breast cancer. This study aimed to evaluate the changes in staging distribution and predictive power of the new staging system. METHODS: Of the 12,275 patients with breast cancer identified from the Severance Breast Cancer Registry who underwent surgery between 1978 and 2016, 12,125 patients met the inclusion criteria. RESULTS: In both the 7th and 8th staging systems, stage I patients constituted the largest proportion (38.2% and 48.4%). Migration from the 7th to 8th edition of the AJCC manual resulted in a decrease in stage II population and an increase in stage I and III populations. A total of 1,293 (15.4%) patients were upstaged, and 1,201 (14.3%) were downstaged. Downstaged patients had better recurrence-free and overall survival (p < 0.001). Pathologic complete response after neoadjuvant therapy showed good prognosis as p stage 0, and yp stages I and III showed poorer outcomes than the same p stage (p < 0.001). CONCLUSIONS: Staging migrations are common in early breast cancer under the prognostic staging system. The prognostic staging system of the 8th edition of the AJCC manual discriminates survival outcomes better than the anatomical staging system of the 7th edition of the AJCC manual.

Coping style at diagnosis and its association with subsequent health-related quality of life in women with breast cancer: A 3-year follow-up study.

PURPOSE: The aim of this study was to describe distinct coping styles of women newly diagnosed with breast cancer and to determine whether there is an association between those styles and the women's long-term health-related quality of life (HRQOL). METHODS: Using a prospective longitudinal study design, we enrolled 101 women recently diagnosed with breast cancer in South Korea and asked them to complete a questionnaire that included the Mini-Mental Adjustment to Cancer (Mini-MAC) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). RESULTS: From the baseline data, we identified two coping style clusters. The first ("FS cluster") had higher scores on the fighting spirit subscale and lower scores on the helpless-hopeless and anxious preoccupation subscales (n = 52, 51.5%), while the second ("HHAP cluster") scored higher on the helpless-hopeless and anxious preoccupation subscales and lower on the fighting spirit subscale (n = 49, 48.5%). In the longitudinal analysis, the FS cluster had a better HRQOL then the HHAP cluster for 2 years after diagnosis, but the HRQOLs did not differ significantly 3 years after diagnosis. CONCLUSIONS: Maladaptive coping at diagnosis may predict poor HRQOL in women with breast cancer. Regular screening of coping style and interventions to improve poor coping style should be considered for at least 2 years post initial diagnosis.

Pre-post analysis of a social capital-based exercise adherence intervention for breast cancer survivors with moderate fatigue: a randomized controlled trial.

PURPOSE: This study assessed the effectiveness of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), regarding cancer-related fatigue (CRF), quality of life (QOL), physical activity, and psychosocial characteristics. METHODS: Forty-eight BCS with moderate or high (≥ 4) CRF participated in this randomized control trial (intervention group n = 23, control group n = 25). The intervention group participated in small group sessions to activate social capital while targeting CRF in supervised physical exercises supplemented by home-based physical exercises. The control group was only given written information on exercise. A questionnaire was used to assess CRF, QOL, physical activity, depression, anxiety, sleep quality, and social capital. RESULTS: The majority of participants had undergone surgery less than 2 years ago. After participating in BLESS, the CRF behavioral/severity domain significantly decreased (t = 2.642, p = 0.011) and physical activity significantly increased (t = - 2.049, p = 0.046) in the intervention group, in comparison with the control group; there were no significant post-intervention differences in the control group. Both groups showed improvements in sleep quality, depression, anxiety, and QOL. CONCLUSION: The BLESS program decreased behavioral/severity in the CRF and increased physical activity after 12 weeks among BCS. Future research needs to evaluate whether the promising results on physical activity and behavioral fatigue observed in the short term will persist over time. Also, longer-term effects should be examined.

Optimal treatment of pseudoangiomatous stromal hyperplasia of the breast.

BACKGROUND: Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. Owing to the rarity of PASH, the pathogenesis, clinical manifestation, and optimal treatment of this condition remain unclear. We aimed to clarify the appropriate management of PASH. METHODS: We performed a retrospective analysis of the clinicopathological data of 66 cases with a diagnosis of PASH, confirmed by core needle biopsy (CNB) or surgical excision at Severance Hospital between 2000 and 2016. The primary endpoint was pathologic results after surgical excision of the lesion that confirmed PASH by CNB. The secondary endpoint was progression after the first treatment. RESULT: The median age of patients was 41 years (range, 14-61 years). Findings on medical imaging were nonspecific. CNB was performed in 61 cases, with a diagnosis of PASH confirmed in 39 cases (63.9%). No malignant or premalignant cells directly arising from PASH were identified after surgical excision that confirmed PASH via CNB. The progression rate after the first treatment was 16.6%, with lesion size, enlargement of palpable mass size, and a diagnosis other than PASH on CNB being factors associated with progression. CONCLUSION: CNB is sufficient to confirm PASH what is necessary for an abnormal imaging or suspicious physical examination finding. Surgical excision is not necessarily indicated to rule out occult malignancy after a diagnosis of PASH. Close monitoring or surgical excision are required to manage large lesions (>3 cm) or progressive growth of a PASH lesion.

Intermediate HER2 expression is associated with poor prognosis in estrogen receptor-positive breast cancer patients aged 55 years and older.

PURPOSE: An antibody-drug conjugate targeting HER2, DS8201, has shown clinical activity against breast cancer with low-level HER2 expression. We aimed to evaluate the prognostic impact of intermediate HER2 expression in estrogen receptor (ER)+ early breast cancer (EBC) and metastatic breast cancer (MBC) cohorts. METHODS: We analyzed prospectively collected data from EBC and MBC cohorts at Yonsei Cancer Center. Patients with HER2 immunohistochemistry (IHC) 0 ~ 1+ were assigned to the HER2-negative group, and patients with IHC 2+ and in situ hybridization (ISH)-negativity were assigned to the HER2-intermediate group. After the exclusion of HER2 IHC 3+ or ISH+ patients, a total of 2657 EBC and 535 MBC patients were analyzed. RESULTS: In total, 654 (24.6%) EBC and 166 (31.0%) MBC patients were classified in the HER2-intermediate group. The HER2-intermediate patients more frequently tended to have progesterone receptor (PR)-negativity and higher nuclear grade in the EBC cohort, and showed a higher proportion of patients aged ≥ 55 years compared with the HER2-negative group in the MBC cohort. The HER2-intermediate patients showed significantly poorer recurrence-free survival (RFS) compared to the HER2-negative patients in the EBC cohort (p = 0.044). Notably, intermediate HER2 expression predicted poorer RFS in EBC patients aged ≥ 55 years (hazard ratio 1.95; p = 0.042) in multivariate Cox analysis but did not affect RFS in those aged < 55 years. In line with the EBC cohort results, intermediate HER2 expression predicted poorer overall survival (OS) in MBC patients aged ≥ 55 (hazard ratio 1.45; p = 0.044) without affecting OS of those aged < 55 years. CONCLUSION: Intermediate HER2 expression is an independent predictor of poor prognosis in both ER+ EBC and MBC patients aged ≥ 55 years. The clinical efficacy of new HER2-targeting antibody-drug conjugates needs to be validated in this high-risk subset of ER+ breast cancer patients.