bims-eabrec Biomed News
on Early breast cancer in young women
Issue of 2023–01–22
seven papers selected by
Rakesh Kumar, Swami Rama University
  1. Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer.
  2. Rates of Bilateral Mastectomy in Patients With Early-Stage Breast Cancer.
  3. Adjuvant trastuzumab and vinorelbine for early-stage HER2+ breast cancer.
  4. Pregnancy-associated breast cancer: does timing of presentation affect outcome?
  5. Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial.
  6. Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses.
  7. Polygenic risk scores and breast cancer risk prediction.
  1. Curr Oncol. 2022 Dec 24. 30(1): 261-273
    Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer.
    Matthias Mäurer, Dorothea Schott, Monika Pizon, Sonia Drozdz, Thomas Wendt, Andrea Wittig, Katharina Pachmann.
       BACKGROUND: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients.
    METHODS: Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0-6 weeks prior to and 0-6 weeks after RT using the maintrac® method, and patients were followed over a median period of 8.97 (1.16-19.09) years.
    RESULTS: Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886).
    CONCLUSIONS: Using the maintrac® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment.
    CLINICAL TRIAL REGISTRATION: The trial is registered (2 May 2019) at trials.gov under NCT03935802.
    Keywords:  biomarkers; circulating epithelial tumor cells; early-stage breast cancer; prediction; radiotherapy
    DOI:  https://doi.org/10.3390/curroncol30010021
  2. JAMA Netw Open. 2023 Jan 03. 6(1): e2251348
    Rates of Bilateral Mastectomy in Patients With Early-Stage Breast Cancer.
    Marie Fefferman, Kyra Nicholson, Kristine Kuchta, Catherine Pesce, Katherine Kopkash, Katharine Yao.
      
    DOI:  https://doi.org/10.1001/jamanetworkopen.2022.51348
  3. Ther Adv Med Oncol. 2023 ;15 17588359221146133
    Adjuvant trastuzumab and vinorelbine for early-stage HER2+ breast cancer.
    Shannon McLaughlin, Erika Nakajima, Yael Bar, Jennifer A Hutchinson, Jennifer Shin, Beverly Moy, Steven J Isakoff, Aditya Bardia, Irene Kuter, Laura M Spring.
       Background: The single-arm phase II APT trial established trastuzumab and paclitaxel (TH) as the standard adjuvant regimen for small human epidermal growth factor receptor 2 (HER2+) tumors. However, paclitaxel causes alopecia and has high rates of neuropathy and hypersensitivity reactions. In patients with metastatic HER2+ breast cancer (BC), the combination of trastuzumab and vinorelbine (TV) is effective and well tolerated. There is a need for alternative non-anthracycline/taxane-based regimens for patients with HER2+ early-stage BC, especially for those with contraindications or who wish to avoid side effects of taxane-based regimens. Here we describe our institutional experience with adjuvant TV for patients with early-stage HER2+ BC.
    Methods: Clinicopathological characteristics, treatment details, and outcomes of patients with localized HER2+ BC treated with adjuvant TV from 2007 to 2021 at a large academic medical institution were collected. Study endpoints included invasive disease-free survival (IDFS), overall survival (OS), and safety/tolerability. IDFS and OS were measured from start date of TV treatment to date of event/last follow-up and date of death/last follow-up, respectively.
    Results: A total of 30 patients were treated with TV. All patients received trastuzumab at standard dosing and vinorelbine at a starting dose of 25 mg/m2 either on days 1/8 or on days 1/8/21 (weekly) of a 21-day cycle with four planned cycles. Median age at diagnosis was 59 years (range: 36-81). 90.3% of patients had anatomic pathologic stage IA BC and 9.7% stage IIA BC. Of the 30 patients, 24 of them opted to pursue TV due to concerns related to alopecia, neuropathy, and other toxicities, and 6 switched from treatment with TH to TV due to toxicities. Eight patients experienced neutropenia with no cases of febrile neutropenia. No patients experienced alopecia or long-term neuropathy. With a median follow-up of 68 months (5.7 years), the 5-year IDFS rate was 90.9%, with one local and one distant recurrence. The 5-year OS was 100%.
    Conclusions: Trastuzumab in combination with vinorelbine in the adjuvant, early-stage setting for low-risk HER2+ BC demonstrated clinical efficacy and appeared to be well tolerated. TV warrants further evaluation as an alternative regimen to TH for patients with early-stage HER2+ BC.
    Keywords:  HER2+ breast cancer; HER2-targeted therapy; adjuvant therapy; breast cancer; chemotherapy
    DOI:  https://doi.org/10.1177/17588359221146133
  4. Breast Cancer Res Treat. 2023 Jan 20.
    Pregnancy-associated breast cancer: does timing of presentation affect outcome?
    Angelena Crown, Damian McCartan, Michael A Curry, Sujata Patil, Sabrina Kamer, Shari Goldfarb, Mary L Gemignani.
       PURPOSE: Pregnancy-associated breast cancer (PABC) comprises breast cancer diagnosed during the gestational period or within 12 months postpartum. While the incidence of PABC appears to be increasing, data regarding prognosis remain limited.
    METHODS: Here we evaluate clinicopathologic features, treatments, and clinical outcomes among women with stage 0-III PABC diagnosed between 1992 and 2020. Comparisons were made between women who were diagnosed with PABC during gestation and those who were diagnosed within 12 months postpartum.
    RESULTS: A total of 341 women were identified, with a median age of 36 years (range 25-46). The pregnancy group comprised 119 (35%) women, while 222 (65%) women made up the postpartum group. Clinicopathologic features were similar between groups, with most patients being parous and presenting with stage I and II disease. Treatment delays were uncommon, with a median time from histologic diagnosis to treatment of 4 weeks for both groups. Recurrence-free survival was similar between groups: 67% at 10 years for both. While 10-year overall survival appeared higher in the postpartum group (83% versus 78%, p = 0.02), only the presence of nodal metastases was associated with an increased risk of death (hazard ratio 5.61, 95% CI 2.20-14.3, p < 0.001), whereas timing of diagnosis and receptor profile did not reach statistical significance.
    CONCLUSION: Clinicopathologic features of women with PABC are similar regardless of timing of diagnosis. While 10-year recurrence-free survival is similar between groups, 10-year overall survival is higher among women diagnosed postpartum; however, timing of diagnosis may not be the driving factor in determining survival outcomes.
    Keywords:  Breast cancer; Lactation; Pregnancy; Recurrence; Survival; Young women
    DOI:  https://doi.org/10.1007/s10549-022-06833-8
  5. J Clin Oncol. 2023 Jan 17. JCO2201499
    Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial.
    Corey W Speers, W Fraser Symmans, William E Barlow, Alex Trevarton, Stephanie The, Lili Du, James M Rae, Steven Shak, Rick Baehner, Priyanka Sharma, Lajos Pusztai, Gabriel N Hortobagyi, Daniel F Hayes, Kathy S Albain, Andrew Godwin, Alastair Thompson.
       PURPOSE: Chemotherapy has not demonstrated benefit over adjuvant endocrine therapy alone for postmenopausal patients with node-positive breast cancer with a 21-gene breast recurrence score (RS) of 25 or below (RS ≤ 25). We tested whether combined results from RS and the sensitivity to endocrine therapy (SET2,3) index of endocrine-related transcription (SETER/PR) adjusted for baseline prognostic index (BPI) improve prognostic assessment, and whether SET2,3 predicted benefit from anthracycline-based chemotherapy.
    METHODS: A blinded retrospective clinical validation of SET2,3 in two randomized treatment arms from the SWOG S8814 trial comparing adjuvant anthracycline-based chemotherapy followed by tamoxifen endocrine therapy for 5 years, versus tamoxifen alone. SET2,3 assay was calibrated and measured using whole-transcriptome RNA sequence of tumor samples already tested for RS. The primary end point was disease-free survival (DFS).
    RESULTS: There were 106 events in 283 patients over a median follow-up of 8.99 years. Proportional hazards assumptions were met during the first 5 years only. SET2,3 index and RS were not correlated (r = -0.04) and were independently prognostic (SET2,3: hazard ratio [HR], 0.48 per unit; 95% CI, 0.34 to 0.68; P < .001; RS: HR, 1.28 per 10 units; 95% CI, 1.14 to 1.44; P < .001). SET2,3 index did not predict chemotherapy benefit (interaction P = .77). SET2,3 was high in 93/175 (53%) patients with RS ≤ 25 (concordant low-risk), with 5-year DFS 97%. SET2,3 was low in 55/108 (51%) patients with RS > 25 (concordant high-risk), with 5-year DFS 53%. Both components of SET2,3 index were prognostic after adjustment for RS: SETER/PR (HR, 0.65; 95% CI, 0.46 to 0.92) and BPI (HR, 0.45; 95% CI, 0.31 to 0.64).
    CONCLUSION: SET2,3 index was not correlated with RS, demonstrated additive prognostic performance, and was not chemopredictive in this subset of patients from S8814. The SETER/PR and BPI components of SET2,3 each added prognostic information to RS.
    DOI:  https://doi.org/10.1200/JCO.22.01499
  6. Biomedicines. 2023 Jan 12. pii: 200. [Epub ahead of print]11(1):
    Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses.
    Alaa Siddig, Wan Faiziah Wan Abdul Rahman, Siti Norasikin Mohd Nafi, Sarina Sulong, Maya Mazuwin Yahya, Tengku Ahmad Damitri Al-Astani Tengku Din, Rozaimi Razali, Kamarul Imran Musa.
       BACKGROUND: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial.
    METHODS: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from 13 fresh estrogen receptor (ER)-positive primary breast cancer tissues of untreated patients (7 = young age ≤45 years and 6 = old age ≥55 years). In silico validation for the differentially expressed genes (DEGs) by young-age patients was conducted using The Cancer Genome Atlas (TCGA) database. Next, we analyzed the protein expression encoded by two of the significantly down-regulated genes by young-age patients, Glycine N-acyltransferase-like 1 (GLYATL-1) and Ran-binding protein 3 like (RANBP3L), using immunohistochemical analysis in an independent cohort of 56 and 74 ER-positive pre-therapeutic primary breast cancer tissues, respectively.
    RESULTS: 12 genes were significantly differentially expressed by young-age breast cancers (fold change &gt;2 or &lt;2- with FDR p-value &lt; 0.05). TCGA data confirmed the differential expression of six genes. Protein expression analysis of GLYATL-1 and RANBP3L did not show heterogeneous expression between young and old-age breast cancer tissues. Loss of expression of GLYATL-1 was significantly (p-value 0.005) associated with positive lymph node status. Higher expression of RANBP3L was significantly associated with breast cancers with lower histopathological grades (p-value 0.038).
    CONCLUSIONS: At the transcriptomic level, breast cancer developed in young and old age patients seems homogenous. The variation in the transcriptomic profiles can be attributed to the other clinicopathological characteristics rather than the age of the patient.
    Keywords:  GLYATL-1; RANBP3L; breast cancer; estrogen-receptor-positive; gene expression; transcriptomic profile; young age
    DOI:  https://doi.org/10.3390/biomedicines11010200
  7. Breast. 2023 Jan 10. pii: S0960-9776(23)00003-6. [Epub ahead of print]67 71-77
    Polygenic risk scores and breast cancer risk prediction.
    Eleanor Roberts, Sacha Howell, D Gareth Evans.
      Polygenic Risk Scores (PRS) are a major component of accurate breast cancer risk prediction and have the potential to improve screening and prevention strategies. PRS combine the risk from Single nucleotide polymorphisms (SNPs) associated with breast cancer in Genome Wide Association Studies (GWAS) and explain over 30% of breast cancer heritability. When incorporated into risk models, the more personalised risk assessment derived from PRS, help identify women at higher risk of breast cancer development and enables the implementation of stratified screening and prevention approaches. This review describes the role of PRS in breast cancer risk prediction including the development of PRS and their clinical application. We have also examined the role of PRS within more well-established risk prediction models which incorporate known classic risk factors and discuss the interaction of PRS with these factors and their capacity to predict breast cancer subtypes. Before PRS can be implemented on a population-wide scale, there are several challenges that must be addressed. Perhaps the most pressing of these is the use of PRS in women of non-White European origin, where PRS have been shown to have attenuated risk prediction both in discrimination and calibration. We discuss progress in developing and applying PRS in non-white European populations. PRS represent a significant advance in breast cancer risk prediction and their further development will undoubtedly enhance personalisation.
    Keywords:  Breast; Cancer; Polygenic; Prediction; Prevention; Risk; Scores; screening
    DOI:  https://doi.org/10.1016/j.breast.2023.01.003
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