Byeong Woo Park

Impact of breast cancer diagnosis and treatment on work-related life and factors affecting them

We investigated the impacts of breast cancer diagnosis and treatment on employment status and the ability to perform occupational and housekeeping tasks. We performed a cross-sectional study to compare Korean breast cancer survivors (nxa0=xa01,594) who had been working before cancer diagnosis with a group of 20 to 60-year-old women from the general Korean population (nxa0=xa0415). Employment decreased from 47.6% to 33.2% after cancer treatment. It was significantly smaller relative to the general population (52.1%) [adjusted odds ratio (aOR)xa0=xa01.68; 95% confidence interval (CI): 1.35–2.11). There was an inverse association between employment and low levels of education, low household income, multiple comorbidities, disease stage, and mastectomy. In addition, women who lived with a spouse were more likely to quit working after treatment compared to women who had no spouse. Fatigue and exhaustion were the most frequent difficulties encountered during occupational work (by 46.8% of cancer survivors) and housework (64.6%). Our findings suggest that breast cancer has a greater impact on employment among Korean women than among women in previously studied Western populations. Our data suggest that socio-cultural factors, as well as certain clinical characteristics, influence the decisions of Korean women to return or to not return to work after surviving breast cancer.

A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study

IntroductionAlthough approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.MethodsTo evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.ResultsIn the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).ConclusionsThis study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.

Expression of estrogen receptor-β in normal mammary and tumor tissues: Is it protective in breast carcinogenesis?

Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-β (ERβ) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERβ in BC development and progression. ERβ expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERβ mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERβ mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERβ expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERβ expression. Collectively, ERβ mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.

Attitudes of cancer patients, family caregivers, oncologists and members of the general public toward critical interventions at the end of life of terminally ill patients

Background: Whereas most studies have focused on euthanasia and physician-assisted suicide, few have dealt comprehensively with other critical interventions administered at the end of life. We surveyed cancer patients, family caregivers, oncologists and members of the general public to determine their attitudes toward such interventions. Methods: We administered a questionnaire to four groups about their attitudes toward five end-of-life interventions — withdrawal of futile life-sustaining treatment, active pain control, withholding of life-sustaining measures, active euthanasia and physician-assisted suicide. We performed multivariable analyses to compare attitudes and to identify sociodemographic characteristics associated with the attitudes. Results: A total of 3840 individuals — 1242 cancer patients, 1289 family caregivers and 303 oncologists from 17 hospitals, as well as 1006 members of the general Korean population — participated in the survey. A large majority in each of the groups supported withdrawal of futile life-sustaining treatment (87.1%–94.0%) and use of active pain control (89.0%–98.4%). A smaller majority (60.8%–76.0%) supported withholding of life-sustaining treatment. About 50% of those in the patient and general population groups supported active euthanasia or physician-assisted suicide, as compared with less than 40% of the family caregivers and less than 10% of the oncologists. Higher income was significantly associated with approval of the withdrawal of futile life-sustaining treatment and the practice of active pain control. Older age, male sex and having no religion were significantly associated with approval of withholding of life-sustaining measures. Older age, male sex, having no religion and lower education level were significantly associated with approval of active euthanasia and physician-assisted suicide. Interpretation: Although the various participant groups shared the same attitude toward futile and ameliorative end-of-life care (the withdrawal of futile life-sustaining treatment and the use of active pain control), oncologists had a more negative attitude than those in the other groups toward the active ending of life (euthanasia and physician-assisted suicide).

Molecular Subtypes and Tumor Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer

Objective: Pathologic complete response (pCR) is the most predictive factor for patients with neoadjuvant chemotherapy and we investigated the rate of pCR according to molecular subtypes defined by immunohistochemical staining. Methods: Our subjects comprised 257 breast cancer patients who received 3 cycles of anthracycline/taxane-based neoadjuvant chemotherapy. The patients were classified into 4 subtypes: luminal A, luminal B, HER2 and triple negative. We analyzed the pCR rate and treatment outcome according to these subtypes. Results: Of a total of 257 patients, the pCR rate of luminal A, luminal B, HER2 and triple negative was 3.9, 5.0, 10.5 and 21.1%, respectively (p = 0.001). The 5-year disease-free survival of the pCR group (88.4%) was higher than that of the non-pCR group (65.6%), but it was not significant (p = 0.228). Among patients who have residual disease, the 5-year disease-free survival of luminal A, luminal B, HER2 and triple negative was 64.0, 65.7, 75.2 and 66.5%, respectively (p = 0.243). Triple negative and HER2 subtypes are more sensitive to neoadjuvant chemotherapy. Conclusion: To increase the pCR rate, type-specific approaches according to subtypes, such as an addition of trastuzumab, increasing the number of cycles or a novel regimen, should be considered.

Risk predictors of underestimation and the need for sentinel node biopsy in patients diagnosed with ductal carcinoma in situ by preoperative needle biopsy

Diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy showed a high rate of underestimation of invasiveness, and performing sentinel lymph node biopsy (SLNB) in DCIS patients was controversial.

Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2

BackgroundThe addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR+) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757–62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported.MethodsPatients were randomized (2:1) to 10xa0mg/day EVExa0+xa0EXE or placebo (PBO)xa0+xa0EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety.ResultsOf 143 Asian patients, 98 received EVExa0+xa0EXE and 45 received PBOxa0+xa0EXE. Treatment with EVExa0+xa0EXE significantly improved median PFS versus PBOxa0+xa0EXE among Asian patients by 38xa0% (HRxa0=xa00.62; 95xa0% CI, 0.41–0.94). Median PFS was also improved among non-Asian patients by 59xa0% (HRxa0=xa00.41; 95xa0% CI, 0.33–0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14xa0months for PBOxa0+xa0EXE, and 7.33 versus 2.83xa0months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients.ConclusionAdding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR+/HER2− advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in Ductal Carcinoma in Situ and Invasive Ductal Carcinoma of the Breast

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-β1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-β1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.

Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with cytologically proven node-positive breast cancer at diagnosis.

BackgroundThe performance of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NCT) was investigated in patients with locally advanced breast cancer (LABC).MethodsAfter NCT of 178 patients with cytology-proven axillary/supraclavicular nodes metastasis at the time of diagnosis, SLNB using radioisotope was performed including completion node dissection between 2008 and 2011. The detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were analyzed.ResultsSLNB was successfully performed in 169 (94.9xa0%) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0, 22.0, 75.8, and 87.0xa0%, respectively, and a greater number of retrieved SLNs increased all four of these performance measures. Conversion to node-negative disease was achieved in 69 (40.8xa0%) patients: 24xa0% of patients with the luminal A subtype, 51.6 % of patients with the luminal B, 51.7xa0% of patients with the HER2-enriched, and 58.5xa0% of patients with the triple-negative breast cancer (TNBC) subtype. Luminal B, HER2-enriched, and TNBC subtypes showed comparable responses to NCT; however, the TNBC subtype had a significantly better FNR and accuracy.ConclusionsSLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NCT. However, acceptable performance was noted for locally advanced TNBCs, and thus SLNB might be safely considered in these selected patients.

Unmet Needs of Breast Cancer Patients Relative to Survival Duration

Purpose The present study aims to evaluate the prevalence of unmet needs among breast cancer survivors, to assess the relationships between unmet needs and depression and quality of life, and to explore the extent to which unmet needs of breast cancer patients relate to the time elapsed since surgery. Materials and Methods Among 1,250 eligible patients who participated in the study, 1,084 cases (86.7%) were used for analysis. Clinicopathological and social parameters were reviewed and the Supportive Care Needs Survey, Functional Assessment of Cancer Therapy-Breast cancer instrument, and Beck Depression Inventory were administered. The frequency of unmet needs, the association between unmet needs and depression and/or quality of life (QOL) and the impact of the time elapsed since surgery on the patients unmet needs were analyzed. Results The highest levels of unmet needs were found to be in the health system and information domain. Patients with a survival duration of less than 1 year since surgery showed significantly higher unmet needs in all need domains except the sexuality domain (p<0.001) than participants in the other groups. Patients with a survival duration of 1-3 years also experienced significantly higher psychological and information needs than long-term survivors (>5 years). In addition, unmet needs were significantly associated with depression (p<0.001) and QOL (p<0.001). Conclusion The present study demonstrated that long-term breast cancer survivors had a significantly lower level of unmet needs than patients with survival duration of less than 3 years after surgery and patients with survival duration of less than 1 year since surgery suffered the greatest unmet needs. QOL might be enhanced if interventions are made for specific unmet needs of each patient group.