One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting ...muscle/limb pain and joint pain on the development of AI‐induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.
What's new?
A standard treatment for breast cancer is aromatase inhibitors (AIs), but common adverse events including musculoskeletal pain can cause early discontinuation. This study analyzed the influence of preexisting muscle/limb pain and joint pain on the development of AI‐induced musculoskeletal adverse events. Women without preexisting muscle/limb or joint pain have the greatest increase in pain after starting adjuvant AI therapy. Women with preexisting pain have higher pain scores, but a smaller increase in pain in comparison. The main increase in pain scores takes place in the first 6 months of endocrine treatment, calling for greater physician attention during this time window.
The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular ...matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects.
We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18.
DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without chemotherapy, the prognostic impact of uPA and PAI-1 was enhanced in cases with additional dCK-positivity (triple +). In cases without chemotherapy, triple-positive status was independently prognostic (HR: 9.3 CI: 1.1-75) next to T stage.
uPA and PAI-1 seem to influence the metastatic potential of dCK+ cells, which underlines its important role in tumor progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We retrospectively investigated concordance of EndoPredict (EPclin) with urokinase plasminogen activator and plasminogen activator inhibitor‐1 (uPA/PAI‐1) in 72 breast cancer patients and compared ...the results with grading, molecular subtype and chemotherapy recommendation. Compared to uPA/PAI‐1, EPclin proved to be more conservative concerning correlation with clinicopathological parameters and was significantly associated with the recommendation of adjuvant chemotherapy.
Background: HER-2/neu overexpressionappears to be associated with improved response to anthracycline-based chemotherapy, but its association with response to taxane-based chemotherapy is unclear. In ...this retrospective subset analysis of patients with metastatic breast cancer enrolled in a randomized treatment trial, we investigated the response of patients with known HER-2/neu status to treatment with taxane-based epirubicin–paclitaxel (ET) chemotherapy compared with treatment with epirubicin–cyclophosphamide (EC) chemotherapy. Methods: HER-2/neu status (positive i.e., HER-2/neu amplification or negative i.e., no HER-2/neu amplification) of archival specimens of primary tumors from 297 patients with metastatic breast cancer was determined by use of fluorescence in situ hybridization. Associations between HER-2/neu status and the efficacy of randomly assigned chemotherapy (ET versus EC) were investigated. All statistical tests were two-sided. Results: Patients with HER-2/neu–positive tumors had a statistically significantly greater objective response rate than patients with HER-2/neu–negative tumors to treatment with ET (76% versus 50%, respectively; P = .005) but not to treatment with EC (46% versus 33%; P = .130). The objective response rate associated with ET was greater than that associated with EC for both HER-2/neu–positive tumors (76% versus 46%; P = .004) and HER-2/neu–negative tumors (50% versus 33%; P = .002). However, the improvement in the objective response rate associated with ET, compared with that associated with EC, was greater for patients with HER-2/neu–positive tumors (adjusted odds ratio OR = 3.64, 95% confidence interval CI = 1.48 to 8.92; P= .005) than for patients with HER-2/neu–negative tumors (adjusted OR = 1.92, 95% CI = 1.01 to 3.64; P= .046). Among patients with HER-2/neu–positive tumors, those who received ET had better progression-free survival and overall survival than those who received EC (for progression-free survival, adjusted relative risk RR = 0.65, 95% CI = 0.42 to 1.02; P= .062; for overall survival, adjusted RR = 0.60, 95% CI = 0.36 to 1.02; P= .059). However, among patients with HER-2/neu–negative tumors, those who received ET and those who received EC had similar progression-free survival and overall survival. Conclusions: HER-2/neu amplification does not adversely influence response to first-line chemotherapy with either ET or EC. Furthermore, a taxane-containing regimen such as ET may provide a preferential benefit to patients with HER-2/neu–positive tumors.
Abstract
While premenopausal patients with HR+ HER2− early breast cancer are treated with tamoxifen +/− ovarian suppression with a GnRH analog or an aromatase inhibitor (AI) + GnRH, the majority
of ...postmenopausal women receive an AI due to its higher efficacy compared to tamoxifen. As the introduction of CDK4/6 inhibitors into the treatment of early-stage breast cancer with a
higher risk of recurrence will probably result in a shift in the endocrine treatment landscape, the question is what treatment did potential candidates for CDK4/6 inhibitors in Germany
receive before CDK4/6 inhibitors were available.
As part of a retrospective multicenter analysis, anonymized data were collected of patients with HR+ HER2− early-stage breast cancer who received endocrine therapy in the period between
10/2021 and 03/2022. Potential candidates for CDK4/6 inhibitor treatment were classified into different risk cohorts using the inclusion criteria of the NATALEE and monarchE trials.
The data of 238 patients from 29 different centers were analyzed. While 20.6% of patients met the monarchE criteria, the subgroup which met the NATALEE inclusion criteria consisted of
46.2% of patients. 53.8% of patients did not meet the inclusion criteria for either the NATALEE or the monarchE trial. More than half of the patients did not receive chemotherapy. 28.6% of
patients in the whole cohort were premenopausal. 67.6% of premenopausal women received neo-/adjuvant chemotherapy. 61.8% of premenopausal patients received tamoxifen as adjuvant endocrine
therapy, 19.1% received an AI + GnRH and 10.3% were treated with tamoxifen + GnRH.
Despite the high percentage of premenopausal patients who received aggressive treatment in the form of chemotherapy, only one third of premenopausal patients received GnRH in addition to
their standard endocrine therapy. Studies carried out at a later point in time and registry studies will be necessary to see how the endocrine therapy landscape in Germany has changed
following the introduction of CDK4/6 inhibitors.
Zusammenfassung
Während prämenopausale Patientinnen mit einem HR+ HER2− frühen Mammakarzinom mit Tamoxifen +/− ovarielle Suppression mit einem GnRH-Analogon oder einem Aromataseinhibitor (AI) + GnRH
behandelt werden, erhalten postmenopausale Frauen vorwiegend einen AI aufgrund der besseren Wirksamkeit verglichen mit Tamoxifen. Da es durch den Einzug der CDK4/6-Inhibitoren in die
Behandlung des frühen Mammakarzinoms mit höherem Rückfallrisiko vermutlich zu einer Verschiebung der endokrinen Therapielandschaft kommt, ist von Interesse, wie in Deutschland potenzielle
CDK4/6-Inhibitor-Kandidat*innen vor deren Markteinführung behandelt wurden.
Im Rahmen einer retrospektiven, multizentrischen Analyse wurden anonymisierte Daten von Patient*innen mit einem HR+ HER2− frühen Mammakarzinom und einer im Zeitraum zwischen
10/2021–03/2022 begonnenen Antihormontherapie erhoben. Potenzielle CDK4/6-Inhibitor-Kandidat*innen wurden anhand der Einschlusskriterien der NATALEE- und monarchE-Studien in entsprechende
Risikokollektive unterteilt.
Insgesamt wurden Daten von 238 Patient*innen aus 29 Zentren analysiert. Während den monarchE-Kriterien 20,6% der Patient*innen zugeordnet werden konnten, enthielt das NATALEE-ähnliche
Kollektiv 46,2% der Patient*innen. 53,8% der Patient*innen erfüllten weder die Einschlusskriterien der NATALEE- noch die der monarchE-Studie. Über die Hälfte der Patient*innen erhielt
keine Chemotherapie. Im Gesamtkollektiv waren 28,6% der Patientinnen prämenopausal. 67,6% der prämenopausalen Frauen wurden mit einer neo-/adjuvanten Chemotherapie behandelt. 61,8% der
prämenopausalen Patientinnen erhielten als adjuvante Antihormontherapie Tamoxifen, 19,1% AI + GnRH und 10,3% Tamoxifen + GnRH.
Trotz des hohen Anteils prämenopausaler Patientinnen, die mit einer aggressiven Therapie im Sinne einer Chemotherapie behandelt wurden, wurde bei nur einem Drittel der prämenopausalen
Patientinnen GnRH zur Antihormontherapie hinzugenommen. Untersuchungen zu einem späteren Zeitpunkt sowie Registerstudien sind nötig, um zu sehen, wie sich durch den Einzug der
CDK4/6-Inhibitoren die endokrine Therapielandschaft in Deutschland verändert.
IntroductionWhile premenopausal patients with HR+ HER2- early breast cancer are treated with tamoxifen +/- ovarian suppression with a GnRH analog or an aromatase inhibitor (AI) + GnRH, the majority ...of postmenopausal women receive an AI due to its higher efficacy compared to tamoxifen. As the introduction of CDK4/6 inhibitors into the treatment of early-stage breast cancer with a higher risk of recurrence will probably result in a shift in the endocrine treatment landscape, the question is what treatment did potential candidates for CDK4/6 inhibitors in Germany receive before CDK4/6 inhibitors were available.Patients and MethodsAs part of a retrospective multicenter analysis, anonymized data were collected of patients with HR+ HER2- early-stage breast cancer who received endocrine therapy in the period between 10/2021 and 03/2022. Potential candidates for CDK4/6 inhibitor treatment were classified into different risk cohorts using the inclusion criteria of the NATALEE and monarchE trials.ResultsThe data of 238 patients from 29 different centers were analyzed. While 20.6% of patients met the monarchE criteria, the subgroup which met the NATALEE inclusion criteria consisted of 46.2% of patients. 53.8% of patients did not meet the inclusion criteria for either the NATALEE or the monarchE trial. More than half of the patients did not receive chemotherapy. 28.6% of patients in the whole cohort were premenopausal. 67.6% of premenopausal women received neo-/adjuvant chemotherapy. 61.8% of premenopausal patients received tamoxifen as adjuvant endocrine therapy, 19.1% received an AI + GnRH and 10.3% were treated with tamoxifen + GnRH.ConclusionDespite the high percentage of premenopausal patients who received aggressive treatment in the form of chemotherapy, only one third of premenopausal patients received GnRH in addition to their standard endocrine therapy. Studies carried out at a later point in time and registry studies will be necessary to see how the endocrine therapy landscape in Germany has changed following the introduction of CDK4/6 inhibitors.
Purpose
Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between ...epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients.
Methods
The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients’ diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test.
Results
In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively).
Conclusions
This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.
The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer ...based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.
Abstract
The Advanced Breast Cancer Fifth International Consensus Conference (ABC5) which focuses on the diagnosis and treatment of advanced breast cancer was held in Lisbon on November 14 – 16, ...2019. The aim of the conference is to standardize the treatment of advanced breast cancer worldwide using evidence-based data and to ensure that patients with advanced breast disease anywhere in the world are treated appropriately and have access to the latest therapies. This year, the emphasis was on new developments and study results from patients with advanced breast cancer as well as precision medicine. The collaboration with patient advocates from all over the globe is also an important goal of the ABC Conference, which is why the international ABC panel also included a number of patient advocates. We present a commentary on the voting results of the ABC5 panelists in Lisbon by a working group of German breast cancer specialists together with the implications for routine clinical care in Germany. The commentary is based on the recommendations of the Breast Commission of the German Gynecological Oncology Working Group (AGO). This commentary is useful, it includes country-specific features for the ABC consensus.
Zusammenfassung
Vom 14. bis 16. November 2019 fand in Lissabon die fünfte internationale Konsensuskonferenz ABC5 (Advanced Breast Cancer Fifth Consensus) zu Diagnostik und Behandlung des fortgeschrittenen Mammakarzinoms statt. Ziel ist es, die Behandlung der Patientinnen mit fortgeschrittenem Mammakarzinom weltweit auf evidenzbasierter Grundlage zu standardisieren und sicherzustellen, dass Patientinnen überall auf der Welt adäquat behandelt werden und Zugang zu neuen Therapien erhalten. Ein inhaltlicher Schwerpunkt lag dieses Jahr auf neuen Entwicklungen und Studienergebnissen beim fortgeschrittenen Mammakarzinom sowie der Präzisionsmedizin. Zudem ist die Zusammenarbeit mit den Patientenvertreterinnen aus aller Welt ein wichtiges Anliegen der ABC-Konferenz, weshalb in dem international zusammengesetzten ABC-Panel auch Patientenvertreterinnen sind. Im vorliegenden Manuskript werden die Abstimmungsergebnisse der ABC5-Panelisten vor Ort durch eine Arbeitsgruppe deutscher Brustkrebsexperten für den Therapiealltag in Deutschland kommentiert. Der Kommentierung liegen die Empfehlungen der Arbeitsgemeinschaft gynäkologische Onkologie (AGO), Kommission „Mamma“ zugrunde. Sie erscheint sinnvoll, da in den ABC-Konsensus auch länderspezifische Besonderheiten einfließen.