Real-world analysis of disease progression after CDK 4/6 inhibitor (CDKi) therapy in patients with hormone receptor positive (HR+)/HER2- metastatic breast cancer (MBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13030-e13030
Author(s):  
Malinda West ◽  
Andy Kaempf ◽  
Shaun Goodyear ◽  
Thomas Kartika ◽  
Jessica Ribkoff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Molecular Characteristics ◽  
Rapid Progression ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Metastatic Setting ◽  
Increased Risk ◽  
Visceral Disease

e13030 Background: CDKi with endocrine therapy (ET) is approved treatment of metastatic HR+/HER2- breast cancer based on PFS benefit vs ET alone. Outcomes data following CDKi discontinuation (dc) is limited, with trials ongoing in this setting. The reported phenomenon of rapid progression within 4 months of CDKi dc raises concern over CDKi impact on HR+/HER2- MBC biology. This study aims to define outcomes after CDKi dc and identify predictors of progression. Methods: This is a retrospective review of women ≥18 years with HR+/HER2- MBC who received CDKi between 4/1/14 and 12/1/19. Patient and tumor characteristics, pre and post CDKi tx, and reason for CDKi dc were collected. Time to event outcomes from date of CDKi dc (primary = PFS, secondary = Overall Survival, OS) were analyzed with Kaplan Meier estimators and Cox regression. Results: Analysis included 140 patients (median age 65 years), with most MBC (84%) arising from earlier stage disease. 51% of MBCs had visceral disease, and 66% received tx prior to CDKi. The most common CDKi was palbociclib (93%); and most common ET were letrozole (52%) and fulvestrant (40%). Median CDKi tx duration was 9 months (3.5 – 17.4) with 80% dc due to progression. Post CDKi txs included chemotherapy (44%), ET (24%), targeted tx (21%), no further tx (7%) and CDKi tx (4%). Median follow up was 12 months. mPFS post CDKi dc were 6.5 months (95% CI: 5.0 – 7.9) and 11.3 months (95% CI: 4.6 – 23.7) in patients who dc CDKi due to progression or other reasons, respectively (HR 1.77, 95%CI: 1.10-2.85). Among 112 patients who progressed on CDKi, estimated 4-month incidence of post CDKi progression or death was 31% (Table ). mOS post CDKi dc was 15.4 months (95%CI: 13.3-19.0) and mOS post CDKi initiation was 26.5 months (95% CI: 23.3 – 34.3). Visceral disease (HR 1.45, 95%CI: 1.01-2.08) and progression as reason for CDKi dc (HR 1.77, 95%CI: 1.1-2.85) were predictors of PFS (p < 0.05). Receiving fulvestrant with CDKi (HR 1.42, 95%CI: 0.96-1.0), prior chemotherapy in the metastatic setting (HR = 1.39, 95% CI: 0.90 – 2.14), and shorter CDKi duration were associated with non-significant increased risk of PFS. Conclusions: Rapid progression or death at 4 months occurred in 31% of MBCs following CDKi dc due to progression. Ongoing studies to define clinical and molecular characteristics of rapidly progressing tumors are underway to develop targeted tx approaches and improve outcomes.[Table: see text]

scholarly journals Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99

2019 ◽  
Author(s):  
Serenella Eppenberger-Castori ◽  
Dirk Klingbiel ◽  
Thomas Ruhstaller ◽  
Daniel Alexander Rufle ◽  
Karin Rothgiesser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Optimal Time ◽  
Her2 Breast Cancer ◽  
Baseline Levels ◽  
Visceral Disease ◽  
Trastuzumab Monotherapy

Abstract Background The HER2 extracellular domain shed in blood (HER2ECD) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods Quantitative assessment of plasma HER2ECD was performed in 133 patients at baseline; after 2-24 hours; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated. Results Baseline HER2ECD levels were stable within 24 hours after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (rs=0.39, P<0.001) and HER2 protein expression levels (rs=0.36, P<0.001) but not with ER/PR status of the primary tumor. HER2ECD baseline levels were positively associated with the presence of visceral disease (P=0.05) and poor patients’ outcome (Cox-regression: P=0.009). Patients with high baseline levels (>35ng/ml) had the worst overall survival (P=0.03) if treated with upfront combination therapy. Conversely, patients with low HER2ECD baseline values (<15ng/ml) had longer TTP-TChemo when first treated with trastuzumab monotherapy (P=0.02). Monitoring HER2ECD levels during the course of the trial revealed significant time (P=0.001) and time-treatment arm interactions (P=0.0007). Under upfront trastuzumab alone, the HER2ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2ECD levels decreased to >20%. Conclusions Plasma HER2ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

scholarly journals Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99.

2020 ◽  
Author(s):  
Serenella Eppenberger-Castori ◽  
Dirk Klingbiel ◽  
Thomas Ruhstaller ◽  
Daniel Dietrich ◽  
Daniel Alexander Rufle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Optimal Time ◽  
Her2 Breast Cancer ◽  
Baseline Levels ◽  
Visceral Disease ◽  
Trastuzumab Monotherapy

Abstract Background: The HER2 extracellular domain shed in blood (HER2ECD) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods : Quantitative assessment of plasma HER2ECD was performed in 133 patients at baseline; after 2-24 hours; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated.Results: Baseline HER2ECD levels were stable within 24 hours after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (rs=0.39, P<0.001) and HER2 protein expression levels (rs=0.36, P<0.001) but not with ER/PR status of the primary tumor. HER2ECD baseline levels were positively associated with the presence of visceral disease (P=0.05) and poor patients’ outcome (Cox-regression: P=0.009). Patients with high baseline levels (>35ng/ml) had the worst overall survival (P=0.03) if treated with upfront combination therapy. Conversely, patients with low HER2ECD baseline values (<15ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy (P=0.02). Monitoring HER2ECD levels during the course of the trial revealed significant time (P=0.001) and time-treatment arm interactions (P=0.0007). Under upfront trastuzumab alone, the HER2ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2ECD levels decreased to >20%. Conclusions: Plasma HER2ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

scholarly journals Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99

2020 ◽  
Author(s):  
Serenella Eppenberger-Castori ◽  
Dirk Klingbiel ◽  
Thomas Ruhstaller ◽  
Daniel Dietrich ◽  
Daniel Alexander Rufle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Optimal Time ◽  
Her2 Breast Cancer ◽  
Baseline Levels ◽  
Visceral Disease ◽  
Trastuzumab Monotherapy

Abstract Background The HER2 extracellular domain shed in blood (HER2 ECD ) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2 ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods Quantitative assessment of plasma HER2 ECD was performed in 133 patients at baseline; after 2-24 hours; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated. Results Baseline HER2 ECD levels were stable within 24 hours after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (r s =0.39, P <0.001) and HER2 protein expression levels (r s =0.36, P <0.001) but not with ER/PR status of the primary tumor. HER2 ECD baseline levels were positively associated with the presence of visceral disease ( P =0.05) and poor patients’ outcome (Cox-regression: P =0.009). Patients with high baseline levels ( > 35ng/ml) had the worst overall survival ( P =0.03) if treated with upfront combination therapy. Conversely, patients with low HER2 ECD baseline values (<15ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy ( P =0.02). Monitoring HER2 ECD levels during the course of the trial revealed significant time ( P =0.001) and time-treatment arm interactions ( P =0.0007). Under upfront trastuzumab alone, the HER2 ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2 ECD levels decreased to > 20%. Conclusions Plasma HER2 ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2 ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

scholarly journals Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99

2019 ◽  
Author(s):  
Serenella Eppenberger-Castori ◽  
Dirk Klingbiel ◽  
Thomas Ruhstaller ◽  
Daniel Dietrich ◽  
Daniel Alexander Rufle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Optimal Time ◽  
Her2 Breast Cancer ◽  
Baseline Levels ◽  
Visceral Disease ◽  
Trastuzumab Monotherapy

Abstract Background The HER2 extracellular domain shed in blood (HER2 ECD ) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2 ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods Quantitative assessment of plasma HER2 ECD was performed in 133 patients at baseline; after 2-24 hours; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated. Results Baseline HER2 ECD levels were stable within 24 hours after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (r s =0.39, P <0.001) and HER2 protein expression levels (r s =0.36, P <0.001) but not with ER/PR status of the primary tumor. HER2 ECD baseline levels were positively associated with the presence of visceral disease ( P =0.05) and poor patients’ outcome (Cox-regression: P =0.009). Patients with high baseline levels ( > 35ng/ml) had the worst overall survival ( P =0.03) if treated with upfront combination therapy. Conversely, patients with low HER2 ECD baseline values (<15ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy ( P =0.02). Monitoring HER2 ECD levels during the course of the trial revealed significant time ( P =0.001) and time-treatment arm interactions ( P =0.0007). Under upfront trastuzumab alone, the HER2 ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2 ECD levels decreased to > 20%. Conclusions Plasma HER2 ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2 ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

scholarly journals Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99

2020 ◽  
Author(s):  
Serenella Eppenberger-Castori ◽  
Dirk Klingbiel ◽  
Thomas Ruhstaller ◽  
Daniel Dietrich ◽  
Daniel Alexander Rufle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Optimal Time ◽  
Her2 Breast Cancer ◽  
Baseline Levels ◽  
Visceral Disease ◽  
Trastuzumab Monotherapy

Abstract Background The HER2 extracellular domain shed in blood (HER2 ECD ) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2 ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods Quantitative assessment of plasma HER2 ECD was performed in 133 patients at baseline; after 2-24 hours; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated. Results Baseline HER2 ECD levels were stable within 24 hours after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (r s =0.39, P <0.001) and HER2 protein expression levels (r s =0.36, P <0.001) but not with ER/PR status of the primary tumor. HER2 ECD baseline levels were positively associated with the presence of visceral disease ( P =0.05) and poor patients’ outcome (Cox-regression: P =0.009). Patients with high baseline levels ( > 35ng/ml) had the worst overall survival ( P =0.03) if treated with upfront combination therapy. Conversely, patients with low HER2 ECD baseline values (<15ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy ( P =0.02). Monitoring HER2 ECD levels during the course of the trial revealed significant time ( P =0.001) and time-treatment arm interactions ( P =0.0007). Under upfront trastuzumab alone, the HER2 ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2 ECD levels decreased to > 20%. Conclusions Plasma HER2 ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2 ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

Treatment and risk of mortality for 58,953 cases of stage 1, ER+/PR+/HER2- breast cancer in four mutually exclusive race/ethnicities.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12101-e12101
Author(s):  
Vincent Caggiano ◽  
Carol Parise
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
White Women ◽  
Cox Regression ◽  
Treatment Modalities ◽  
Her2 Breast Cancer ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Race Ethnicity ◽  
Stage 1

e12101 Background: The estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor 2 negative (HER2-) subtype is the most common. Cases of stage 1, ER+/PR+/HER2- are most often treated with hormone therapy alone, although this is not universal. The purpose of this study was to determine if there were differences in mortality for patients with stage 1, ER+/PR+/HER2- breast cancer given no treatment, chemotherapy alone, or both chemotherapy and hormone therapy when compared with hormone therapy alone for four mutually exclusive race/ethnicities. Methods: We identified 58,953cases of Stage 1, ER+/PR+/HER2- first primary female invasive breast cancer from the California Cancer Registry 2000-2014. Cases were stratified into white (n = 41,716), black (n = 2,310), Hispanic (n = 8,186) and Asian/Pacific Islander (API) (n = 6,741). Treatment was categorized as none, hormone therapy alone, chemotherapy alone, or both chemotherapy and hormone therapy. Kaplan Meier survival analysis and Cox Regression were used to assess the risk of mortality associated with treatment using hormone therapy alone as the reference category. Treatment was considered a risk for mortality and hazard ratios (HR) and 95% confidence intervals reported if the Wald χ2 was statistically significant (p < 0.05). Models were adjusted for age, grade, socioeconomic status, and tumor size. Separate analyses were conducted for each race/ethnicity. Results: White women, having no treatment (HR = 1.33; 1.14-1.54), or chemotherapy alone (HR = 1.49; 1.10-2.00) was associated with an increased risk of mortality. For API women, having the combination of chemotherapy and hormone therapy was associated with increased risk of mortality (HR = 2.47; 1.34-4.56). For black and Hispanic women, there was no difference in risk of morality for any combination of treatment when compared with hormone therapy. Conclusions: The effectiveness of treatment modalities for the Stage 1, ER+/ER+/HER2- subtype varies considerably by race/ethnicity.

scholarly journals Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3735
Author(s):  
Hara Polioudaki ◽  
Anastasia Mala ◽  
Eleni Gkimprixi ◽  
Maria A. Papadaki ◽  
Amanda Chantziou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Mononuclear Cells ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

We aimed to evaluate the co-expression of PD-L1 and epithelial-mesenchymal markers in CTCs from metastatic breast cancer (MBC) patients and to determine if there is any relationship with patients’ outcome after eribulin treatment. Using cytospin preparations of peripheral blood mononuclear cells (PBMCs) from MBC patients treated with eribulin and a combination of immunocytochemistry and immunofluorescence, we quantified PD-L1, keratins and vimentin in single and cluster CTCs on days 1 and 8 of the first-treatment cycle. CTCs (n = 173) were found in 31 out of 38 patients. At baseline, the presence of cluster CTCs (p = 0.048), cluster mesenchymal CTCs (mCTCs) (p = 0.0003) or cluster PD-L1+mCTCs (p = 0.006) was associated with shorter overall survival (OS). In multivariate cox regression analysis, the detection of cluster mCTCs was the only parameter associated with increased risk of death (p = 0.024). On day 8 post-eribulin administration, PD-L1+mCTCs and especially single PD-L1+mCTCs decreased in 75% and 89% of patients, respectively. The detection of single PD-L1+mCTCs after eribulin treatment was correlated with shorter PFS (p = 0.047) and OS (p = 0.020). In conclusion, our study identified for the first time that cluster and single PD-L1+mCTCs subpopulations are of clinical significance in patients with MBC and highlighted the importance of CTC phenotyping during treatment with eribulin.

Outcome of palbociclib based therapy in hormone receptor positive metastatic breast cancer patients after treatment with everolimus.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1054-1054 ◽  
Author(s):  
Ajay Dhakal ◽  
Christina Matthews ◽  
Fan Zhang ◽  
Ellis Glenn Levine ◽  
Stephen B. Edge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Benefit ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

1054 Background: Resistance mechanisms to CDK 4/6 inhibition are not well defined. Outcome data on hormone receptor positive (HR+) metastatic breast cancer patients (MBCP) treated with palbociclib (PA) after treatment with everolimus (EV) are lacking. The PALOMA 3 trial (P3) showing benefit of PA plus fulvestrant (FU) compared to FU in HR+ MBCP after progression on endocrine therapy excluded women previously treated with EV. The aim of our study was to investigate the outcomes of HR+ MBCP with prior EV treatment on PA based therapy. Methods: This is a retrospective, single institute review of HR+, HER 2 nonamplified MBCP from Jan 2014 - Nov 2016 treated with PA after treatment with EV. Women who received EV for < 1 month or PA < 14 days were excluded. Progression free survival (PFS) was defined as the time from the initiation of PA to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Response rates were determined based on available radiological data. Clinical benefit was defined as a complete response (CR), partial response (PR) or stable disease of at least 24 weeks. Results: 23 patients with mean age 67 years (42 to 81) were identified. 95% were postmenopausal, 81% had ECOG performance status 0 or 1, 83% had visceral metastases, 95% had > 2 lines of prior endocrine therapy (ET), 82% shown prior sensitivity to ET, 82% received prior chemotherapy, of which 84% were in metastatic setting. Kaplan Meier estimate showed median PFS of 2.9 months (95% CI 2.0-4.2); median PFS of P3 PA cohort was 9.5 months (95% CI 9.2-11.0). Fisher’s exact test comparing study cohort with P3 PA cohort showed statistically significant differences in objective response (CR or PR) rates of 0/23 (0%) vs. 66/347 (19%, p = 0.02) & clinical benefit ratio of 4/23 (17.4%) vs. 231/347 (66.5%, p = 0.00). Conclusions: Outcomes with PA in HR+ EV treated MBCP were worse when compared to the P3 PA cohort data. Treatment with EV may lead to resistance to CDK inhibition. Though limited by size, our data suggests that use of PA after EV is associated with low response & clinical benefit rates. Further studies are necessary to confirm the findings to determine sequencing of targeted therapies.

scholarly journals Incidence of hypothyroidism after treatment for breast cancer—a Danish matched cohort study

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Anne Mette Falstie-Jensen ◽  
Buket Ö. Esen ◽  
Anders Kjærsgaard ◽  
Ebbe L. Lorenzen ◽  
Jeanette D. Jensen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Cancer Treatment ◽  
Cumulative Incidence ◽  
Breast Cancer Survivors ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Incidence Rates ◽  
Diagnostic Codes ◽  
Increased Risk

Abstract Background Breast cancer survivors (BCS) may have increased risk of hypothyroidism, but risk according to treatment modality is unclear. We estimated the incidence of hypothyroidism in women with breast cancer, and according to cancer treatment. Methods Using nationwide registries, we identified all Danish women aged ≥ 35 years diagnosed with non-metastatic breast cancer (1996–2009). We matched up to five cancer-free women (controls) for each BCS. We excluded women with prevalent thyroid disease. Cancer treatment was chemotherapy with or without radiotherapy (RT) targeting the breast/chest wall only, or also the lymph nodes (RTn). We identified hypothyroidism using diagnostic codes, and/or levothyroxine prescriptions. We calculated the cumulative incidence, incidence rates (IR) per 1000 person-years, and used Cox regression to estimate hazard ratios (HR) and associated 95% confidence intervals (CIs) of hypothyroidism, adjusting for comorbidities. Results We included 44,574 BCS and 203,306 matched controls with 2,631,488 person-years of follow-up. BCS had a slightly higher incidence of hypothyroidism than controls [5-year cumulative incidence, 1.8% (95%CI = 1.7–1.9) and 1.6% (95%CI = 1.5–1.6), respectively]. The overall IR was 4.45 (95%CI = 4.25–4.67) and 3.81 (95%CI = 3.73–3.90), corresponding to an adjusted HR = 1.17 (95%CI = 1.11–1.24). BCS who received RTn with chemotherapy (HR = 1.74, 95%CI = 1.50–2.02) or without chemotherapy (HR = 1.31, 95%CI = 1.14–1.51) had an elevated risk of hypothyroidism compared with matched controls and compared with BCS who underwent surgery alone [HR = 1.71, 95%CI = 1.45–2.01 and HR = 1.36, 95%CI = 1.17–1.58, respectively]. Conclusions BCS have an excess risk of hypothyroidism compared with age-matched controls. BCS and those working in cancer survivorship settings ought to be aware that this risk is highest in women treated with radiation therapy to the lymph nodes and chemotherapy.

scholarly journals Role of palbociclib in the treatment of hormone receptor-positive HER2-negative metastatic breast cancer. Generalizing results of randomized trials and real clinical practice

2019 ◽  
pp. 56-62
Author(s):  
L. G. Zhukova ◽  
E. I. Khatkova ◽  
P. S. Feoklistova ◽  
K. S. Grechukhina ◽  
S. A. Smolin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Hormone Receptor ◽  
Randomized Trials ◽  
Metastatic Breast ◽  
Second Line Therapy ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Real Clinical Practice

Palbociclib is the first-in-class drug of CDK 4/6 inhibitors group. The use of palbociclib in combination with endocrinotherapy (ET) opens up new possibilities for the treatment of metastatic hormone receptor-positive (HRP+) HER2-negative (HER2-) breast cancer (mBC). Palbociclib has gained world attention and is included in all clinical guidelines, both international and domestic, as a new standard of first- and second-line therapy of HRP+ HER2- mBC. The article presents the updated results of PALOMA-2 and PALOMA-3 studies and the results of use of palbociclib in combination with ET in real clinical practice.

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