Adherence to multidisciplinary team meeting recommendations in elderly patients with HER2-positive breast cancer

doi:10.21203/rs.3.rs-3107172/v1

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Research Article

Adherence to multidisciplinary team meeting recommendations in elderly patients with HER2-positive breast cancer

https://doi.org/10.21203/rs.3.rs-3107172/v1

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Purpose

Applying current treatment guidelines to elderly breast cancer (BC) patients is challenged by limited trial guidance, higher toxicities, and non-cancer related mortality. This study investigated adherence to multidisciplinary team meeting (MDTM) recommendations in elderly women with HER2 positive BC (HER2+BC) and its impacts on patient survival.

Methods

This retrospective multicentre cohort study collected data from 305 patients with primary diagnosis of HER2+BC. Women aged ≥65 years were classified into “concordant” or “discordant” groups according to MDTM recommendation adherence. Cox proportional hazards models and logistic regression analysis were used to assess the association between prognostic factors and patient outcomes.

Results

Of 305 HER2+BC patients, 111 (36%) were ≥65 years old. Of these, 55 (49.5%) and 53 (47.7%) were assigned to the concordant or discordant groups, respectively. The most frequent cause of MDTM discordance was treatment rejection by patients (57%). Median age (79 vs 70 years, p = <0.001) and Charlson Comorbidity Index (score 6 vs 5, p = 0.017) were significantly higher in the discordant group. After adjusting for age, UICC stage and hormone receptor status, overall survival (OS; HR 1.49, CI [0.64-3.46], p = 0.36) showed no significant difference between groups with a median follow up of 42.8 months. Patients with pre-existing cardiac diseases (29.6%) had significantly reduced OS (log-rank test p = 0.0082).

Conclusion

Adjustments to MDTMs for older BC patients may be necessary to increase patient treatment acceptance. Moreover, approaches to reduce treatment intensity in selected elderly patients with HER2+BC should be investigated further.

multidisciplinary team meetings

elderly breast cancer patients

HER2 positive breast cancer

geriatric oncology

cancer disparities

cancer treatment outcomes

Approximately 40% of breast cancers (BC) occur in women aged 65 or older, and a significant proportion, 20%, occur in women over 75 [1]. The prevalence of human epidermal growth factor receptor 2 overexpression (HER2+) in elderly BC patients is only slightly lower than the 15–20% rate in patients aged younger than 65 years [2, 3]. Similar to younger BC patients, HER2 + BC in elderly patients demonstrate poor prognostic characteristics, such as higher proliferative Ki-67 presence in the tumour [3]. Consequently, clinical outcomes for elderly BC patients not receiving HER2 targeting therapy is poor, even when the age competing risk of mortality is considered [3–6]. As a result of the ageing population, the number of elderly BC patients is rising. Despite this, elderly patients have been consistently underrepresented in clinical trials [7–9]. Only 16% of patients in the pivotal trials of adjuvant trastuzumab therapy were over 60 years old [10–12]. Set thresholds of chronological age, which define a patient as elderly, also vary from ≥ 65 [13, 14], ≥ 70 [15–17] to ≥ 75 [5, 18] or even ≥ 80 years old [19], which complicates comparisons between studies. Furthermore, older participants in randomised controlled trials (RTCs) may be fitter than the wider elderly population [7–9]. Thus, the application of current treatment recommendations in elderly patients outside clinical trials can be limited due to the cardiotoxic nature of anthracycline-based chemotherapy and HER2-targeted therapy [8, 9, 20–22]. Given the higher risk of toxicities and competing causes of mortality, elderly patients are often less willing to trade a potentially extended lifespan for decreased quality of life (QoL) [23, 24]. Various studies have evaluated approaches to reduce treatment intensity in elderly BC patients [14–16, 25], but there is ongoing discussion regarding whether the elderly population is under- or over-treated, due to a lack of trial guidance and age-based restrictions [6, 9, 14, 19, 26]. Multidisciplinary team meetings (MDTMs), also called tumour board conferences, are standard tools for delivering patient-centred care. However, data on the adherence to MDTM recommendations and the impact on overall survival (OS) in cancer patients is limited, and outcomes can vary between high and low income countries [27–29]. Evidence is particularly lacking in the subset of elderly BC patients with an aggressive tumour biology. As a consequence of MDTMs focusing mainly on cancer pathology, the special needs of elderly BC patients seem to remain underrepresented in MDTMs [30–33]. The objective of this study was to assess the adherence to MDTM recommendations in elderly HER2 + BC patients and examine its impacts on progression free survival (PFS) and OS.

Patient and Data Selection

A multicentre, observational cohort study was undertaken. Consecutive patients ≥ 65 years old with a primary diagnosis of HER + BC between January 2012 and December 2020 at the Breast Cancer Centre University Hospital Basel and University Hospital Zürich were included in the study. Both Breast Cancer Centres are tertiary referral centres in Switzerland and certified by the German Cancer Society and either by the Swiss Cancer Society or Doc-cert. The MDTMs in both centres represent BC-specific tumour board conferences. Within the certification process, it is required that MDTMs take place at least once a week and include the participation of a specialist from breast surgery, radiology, pathology, radiation therapy, plastic surgery, medical and gynaecologic oncology. Patients included in the study were identified from a local database at each Cancer Centre. Detailed data regarding patient demographic, tumour biology, pathological and molecular characteristics, treatment regimen information, disease recurrence and survival outcomes were obtained by retrospective chart review. Concordance or discordance with the MDTM decisions was evaluated by two independent gynecologically-trained examiners based on a retrospective comparison of MDTM report and subsequent treatment plan documentation. Cardiac dysfunction following treatment is defined as a decline in the left ventricular ejection fraction (LVEF) of ≥ 10 percentage points. Geriatric screening was implemented retrospectively using the Charlson Comorbidity Index (CCI)[34] at the time point of diagnosis based on the International Classification of Diseases (ICD) diagnosis codes found in the hospital patient charts data.

Statistical Analysis

Descriptive statistics analysis was used to analyse clinical and demographic characteristics of the study cohort. Descriptive statistics are presented as counts and frequencies for categorical data and median (interquartile range) for metric variables. Overall p values correspond to T-test (for means), Kruskall-Wallis test (for median) and chi-squared or exact Fisher test when the expected frequency is less than 5 in some cells. A p value of < 0.05 was considered statistically significant. Survival curves were estimated using the Kaplan-Meier method and log-rank tests were performed for comparison of survival outcomes. Cox proportional hazards regression models were used to determine prognostic factors of survival and expressed as hazard ratios (HR) with a 95% confidence interval (CI). In order to estimate the dependence of discordance on CCI, logistic regression was performed. Results are presented as odds ratio with 95% confidence interval and p value. All evaluations were made in the statistical software R, version 4.1.3 (2022-03-10).

Patient characteristics

Characteristics of patients in the two population (concordant and discordant to MDTM) including hormone receptor status, Union for International Cancer Control (UICC) stage, co-morbidities and treatment are described in Table 1. Out of 305 patients with a primary diagnosis of HER2 + BC, 111 (36.4%) patients were ≥ 65 years old and, therefore, included in this study. Missing MDTM data in the patient chart was found in only 3 cases (2.7%), which have been categorised as “unknown”. The evaluated study population thus included 108 HER2 + BC patients with a median age of 73 years (Fig. 1).

Median age was significantly higher in the discordant group (79 [65.0;95.0] vs 70 [65.0;85.0] years in the concordant group, p = < 0.001). The entire study population presented a median CCI score of 6 [4.00;14.0], with slightly higher CCI values in the discordant group (median CCI 6 [4.00;13.0] vs 5 [4.00;14.0], p = 0.017) (Supplemental Fig. 1). To determine whether higher CCI was associated with MDTM discordance, a linear logistic regression was performed. An odds ratio (OR) of 1.10 [0.94–1.29, p = 0.215] showed no significant influence of CCI on discordance (Table 1).

Table 1

Patient characteristics of MDTM concordant and discordant groups. Cohort includes all patient ≥ 65 years old who presented with first diagnosis of HER2 + BC at the University hospital of Basel or Zürich between 2012–2020. NST = invasive carcinoma of no special type, ER = oestrogen receptor, PR = progesterone receptor, UICC = Union for International Cancer Control, BC = breast cancer, TDM-1 = trastuzumab emtansine (Kadcyla)
	all (%)	MDMT concordance (%)	MDMT discordance (%)	p value
	N = 108 (100)	N = 55 (50.9)	N = 53 (49.1)
Median age at diagnosis in years	73 [65; 95]	70 [65; 85]	79 [65; 95]	< 0.001
Histology	N = 106			0.224
NST	97 (91.5)	51 (94.4)	46 (88.5)
Lobular	7 (6.6)	2 (3.7)	5 (9.6)
Others	2 (1.9)	0 (0)	1 (1.9)
Hormone receptor status	N = 108			1.000
positive (ER > 1% or/and PR ≥ 5%)	78 (72.2)	40 (72.7)	38 (71.7)
negative	30 (27%)	15 (27.3)	15 (28.3)
UICC stage	N = 106			0.068
Early BC (I-IIB)	69 (65.1)	35 (66.0)	34 (64.2)
Locally advanced BC (IIIA-IIIC)	18 (17.0)	5 (9.43)	13 (24.5)
Metastatic disease (IV)	19 (17.9)	13 (24.5)	6 (11.3)
Comorbidities	N = 108
Pre-existing cardiac disease	32 (29.6)	8 (14.5)	24 (45.3)	0.001
- Coronary heart disease	14 (13.0)	2 (3.64)	12 (22.6)	0.008
- Heart failure	3 (2.78)	1 (1.82)	2 (3.77)	0.614
- Cardiomyopathy	6 (5.56)	3 (5.45)	3 (5.66)	1.000
Hypertension	54 (50.0)	27 (49.1)	27 (50.9)	1.000
Diabetes	15 (13.9)	8 (14.5)	7 (13.2)	1.000
Obesity	7 (6.48)	3 (5.45)	4 (7.55)	0.713
Smokers	23 (25.0)	10 (20.8)	13 (29.5)	0.470
Initial chemotherapy	N = 104			< 0.001
Taxan	26 (25.0)	20 (38.5)	6 (11.5)
Taxan+ Alkylating agents	14 (13.5)	7 (13.5)	7 (13.5)
Anthracycline + Alkylating agents + Taxan	16 (15.4)	15 (28.8)	1 (2.0)
Others	11 (10.5)	5 (9.6)	6 (11.5)
No chemotherapy	37 (35.6)	5 (9.6)	32 (61.5)
Targeted therapy	N = 106			< 0.001
Trastuzumab	53 (50.0)	34 (63.0)	19 (36.5)
Trastuzumab + Pertuzumab	29 (27.4)	17 (31.5)	12 (23.1)
TDM-1	1 (0.9)	0 (0)	1 (0.9)
No targeted therapy	23 (21.7)	3 (5.6)	20 (38.5)
Surgery	N = 100			0.041
BET	48 (48.0)	29 (56.9)	19 (38.8)
Ablatio	32 (31.0)	10 (19.6)	21 (42.9)
No surgery	21 (21.0)	12 (23.5)	9 (18.4)
Radiotherapy	N = 102			0.017
Yes	57 (55.9)	35 (68.8)	22 (43.1)
No	45 (44.1)	16 (31.4)	29 (56.9)

Adherence to MDTM recommendations

Adherence to MDTM recommendations in subsequent treatment plans was determined in 51% of the patients (55/108). To identify any bias in deviations from specific treatment approaches, the types of discordance are categorized as discordance to surgery, chemotherapy, targeted therapy, radiotherapy, and endocrine therapy. The most common deviations were from recommended chemotherapy (63%, 19/108), followed by variations of targeted therapy (13%, 4/108). Within each treatment subgroup, the percentage of patients with treatment discordance to MDTM decision rises with increasing age (Fig. 3). Reasons for discordance included patient rejection, physician’s choice, and adverse events, with treatment rejection by the patient (57%; 29/53) being the primary cause of non-adherence. In nine patients (8.5% (9/108) of the total cohort, or 17% (9/53) of discordant cohort), treatment deviated from the MDTM decision because of the following adverse events: cancer-related death, myocardial infarction, congestive heart failure, renal failure, gastrointestinal bleeding, mucositis, skin toxicity, recurrent chemo-toxic pneumonitis, and diarrhoea. No treatment-related death was recorded.

Survival analysis

Although the main reason for discordant treatment was treatment rejection by the patient, we were unable to observe a statistically significant difference between MDMT concordant vs. discordant groups in PFS (median 49.08 months, p = 0.091) and OS (median 86.45 months, p = 0.17) within a median follow-up time of 42.8 [0.03;108] months. This was confirmed for OS in a Cox regression analysis adjusted to age, UICC stage (I-IIB, IIIA-IIIC and IV) and hormone receptor status (HR 1,48 [0.64;3,43, p = 0.36]).

Furthermore, a separate Kaplan-Meier analysis assessing the impact of adherence to MDMT on OS (p = 0.44) in patients ≥ 80 years of age confirmed no difference between groups (Supplemental Fig. 2).

Cardiac toxicity

Our study population includes 29.6% patients (32/108) with a pre-existing cardiac disease in their medical history. Structured cardiac monitoring by echocardiogram was performed in patients with HER2-targeted treatment (n = 88) at least once before and 12 months after therapy. Baseline cardiac function measured by LVEF was determined in 85.2% (75/88) of the patients with HER2-targeted therapy. Complete cardiac monitoring was performed in 63.6% (56/88) of the relevant patients. In 20.5% (18/88) of patients the 12-month echocardiogram was missing in the patient's records, and in 14.8% (13/88) the cardiac monitoring record was completely absent. No significant difference in cardiac function was found between the two groups at baseline, with a mean LVEF of 61.3% vs 59.6% in the concordant and discordant groups, respectively. After treatment, the delta LVEF notably declined in the subgroup with adherence to MDTM recommendation (mean delta LVEF% -2.455 after treatment vs 1.217 before, p = 0.017, Fig. 5). Cardiac dysfunction occurred in 7.1% of all patients (4/108, including one case of symptomatic congestive heart failure), and one cardiac adverse event (myocardial infarction) (0.9%, 1/108)) was observed. We found a statistically significant reduced OS in patients with a pre-existing cardiac disease (Fig. 6).

Breast cancer is a complex disease, and its management requires complex clinical decision-making. MDTMs, which follow standard operating procedures and guidelines, have been implemented routinely across cancer care services to improve patient management and clinical outcomes. In this study, the investigation of the MDTM reports from 108 elderly patients diagnosed with HER2 + BC and their follow-up treatments showed that discordance to MDTM decisions in this particular subset of patients had no significant impact on OS or PFS. Instead, women with pre-existing cardiac diseases showed worse survival outcomes in our study, independent of their treatment adherence to MDTM recommendations. Thus, investigation of deescalating strategies in elderly patients, and optimization of their MDTM presentation, may help to improve outcomes for this vulnerable group of patients.

Despite recent evidence of elderly and poor prognosis patients being less represented in MDTMs [31], unknown MDTM records only occurred in 2.7% (3/111) of our study, showing high coverage of elderly BC patients in MDTM reviews. However, comorbidities occur frequently among elderly patients, which limits safe delivery and completion of BC treatments. A previous study of 4501 early BC patients showed increasing age (OR 1.68, p = < 0.001), histological grade III (OR 1.3, p = 0.011) and HER2 + status (LuminalB/HER2 + OR 3.125, p = < 0.001 and HER2 + OR 1.772, p = 0.009) to be independently associated with discordance to MDTM recommendation [35]. We could confirm these results in our cohort.

Only half of the patient population was treated in concordance to MDTM recommendations in their subsequent clinical course. The high proportion of women with MDTM discordance in our study, with most deviation related to recommended chemotherapy regimen, is consistent with previously published studies showing that among patients aged 70–85 years, only 56.9% patients received planned adjuvant chemotherapy after MDTM review [36], and that older age correlated with reduced adjuvant chemotherapy application [37]. Furthermore, 47.5% of patients declined chemotherapy if benefits were borderline [38]. Patient preferences thus also had an impact on compliance to MDTM recommendations [38, 39]. Thirty patients within our study rejected MDTM recommended treatment (Fig. 2), mainly chemotherapy and targeted therapy, highlighting that older patients are less likely to trade QoL for length of life [23, 24]. This is in line with the Age Gap trial findings, where Wyld et al. found that use of a decision support tool resulted in elderly women choosing more primary endocrine therapy vs. surgery [40].

In accordance with international guidelines, MDMT decisions should involve geriatric assessments combined with careful consideration of competing risks of mortality and patient preferences [17, 41]. The American Society of Clinical Oncology (ASCO) has proposed comprehensive geriatric assessment for patients ≥ 65 years of age being considered for chemotherapy [42]. Geriatric assessments prior to presentation in MDTMs have been shown to improve care plan establishment [31] However, this can be time consuming and might not be necessary for all older patients [43, 44]. In order to improve the care of elderly BC patients, the International Society of Geriatric Oncology (SIOG) was created in 2007. Their recommendations were revised in 2012 in collaboration with European Society of Breast Cancer Specialists (EUSOMA) and the latest update was published in 2021. SIOG recommends tailored treatment approaches based on the following patient groupings: fit, susceptible and frail [17]. In our cohort, the mean CCI was found to be slightly higher than that reported in other studies [40]. Patients with adherence to MDTM recommendations showed a marginally lower CCI value compared to patients with discordant treatment, although higher CCI scores (under linearity assumption) were not predictive for discordance to MDTM recommendation (OR 1.10 [0.94–1.29, p = 0.215]).

De-escalating strategies in elderly BC patients have been explored previously [14, 16, 20, 25, 45, 46], but in most of these studies a benefit of de-escalating options was only demonstrated in low-risk HER2-negative BC patients. Older BC patients with a high risk of recurrence showed no improvement in OS or BC-specific survival via a de-escalating approach of surgery and endocrine therapy (without adjuvant chemotherapy) [45]. Although adjuvant chemotherapy offers little benefit to most elderly, hormone receptor positive BC patients, benefits have been demonstrated for older women with hormone receptor negative BC. QoL impacts of chemotherapy have also been reported to be significant, but transient [46]. SIGO recommends adjuvant chemotherapy along with one year of trastuzumab as a standard approach in elderly, early-stage, HER2 + BC patients with a tumour size > 0.5cm and normal cardiac function [9, 17]. However, in elderly women, the cardiotoxicity associated with trastuzumab treatment is of particular concern. Trastuzumab increases the risk of declined LVEF, which can clinically manifest as heart failure. Rates of 7.1% (4/108) decrease in LVEF and 0.9% (1/108) cardiac adverse events from our study correlates with reported incidence rates, ranging from 3 to 27% depending on definition, administration time and chaperoning medical treatment [12, 47–51]. Previous studies indicate age as a main risk factor for this treatment-related cardiotoxicity [51–55], with additional risk factors including history of cardiac disease, obesity, diabetes, smokers and dyslipidemic patients, previous anthracycline exposure and previous radiation therapy [56–58]. Indeed, cohort studies estimate an even higher risk for trastuzumab-related cardiotoxicity in older women than those reported in the pivotal trials [21, 59, 60]. Our results showed a worse overall survival for women with pre-existing cardiac disease, and significantly lower deltaLVEF values in the MDTM-concordant group. This reflects the significant effects that cardiotoxic treatments have in patients with cardiac disease and highlights the importance of implementing tools to identify elderly patients with a higher risk of cardiotoxicity. Establishment of routine and structured cardiac monitoring during trastuzumab therapy is critical, especially in this high-risk patient population. The literature generally suggests use of screens every three months combined with echocardiography, or other imaging, for early breast cancer. However, the optimal frequency and type of imaging technique is yet to be determined [58, 61]. Some research has indicated that cardioprotective pharmacological strategies may be beneficial in patients with HER2 + BC [62–64]. However, due to increased comorbidities associated with multidrug treatments, this approach may be limited for older patients. Given that the strength of MDTM recommendations relies on the clinical information available at the time of presentation [38], we propose that cardiac toxicity risk assessments should be included in the MDMT presentation of elderly HER2 + BC patients.

Strength and limitations

The impact of MDTMs on a patient's clinical outcome is mainly studied in populations with and without MDTM presentations. However, adherence to MDTM recommendations and the impacts on patient outcomes are rarely investigated [35, 65, 66], and most previous reports have been in heterogeneous study populations [6, 27–28, 35, 66]. To our knowledge, this is the first study addressing adherence to MDTM recommendations and its impact on survival outcomes in a subset of older HER2 + BC patients. The evaluation of MDTM impacts on real-world disease outcomes offers an opportunity for future research [35, 65] and may help to optimise MDTM presentations. However, our study is limited by retrospective observational design, being underpowered and missing the direct comparisons between older and younger patients. Thus, an adjustment for important cofounders is not possible in this dataset. A Power calculation for a log-rank statistics based on an estimated Hazard ratio of 0.77 calculates a total sample size requirement of 1900 patients (Alpha = 5%, Power = 80%, Follow up: Five years), which is difficult to acquire in this particular subset of patients. Similar to observational studies [7], many elderly patients also did not undergo a complete cardiac assessment, even though it was a requirement for trastuzumab therapy.

Our results suggest that further adjustment of MDTM presentations could improve clinical outcomes for older BC patients. The goal of the MDTM is to achieve the best outcome for a given patient with as few complications as possible. To achieve this, the integration of knowledge from different disciplines, at different points in the treatment process, is crucial. In order to achieve recommendations that are as patient-centred and personalized as possible, we recommend improved inclusion of particular comorbidities, such as cardiac toxicity risk assessments for elderly HER2 + BC patients. In light of our results, approaches to reduce treatment intensity in selected elderly patients with HER2 + BC seem reasonable and should be further evaluated in age-specific BC studies.

Acknowledgment

This work was supported by the Swiss Cancer Research foundation & Swiss Cancer League [KFS-5445-08-2021]. We would also like to thank all the physicians involved in the MDTMs and treatments of the included patients.

Acknowledgment

Funding

Author FG has received research support by the Swiss Cancer Research foundation & Swiss Cancer League [KFS-5445-08-2021].

Competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

CK: Christian Kurzeder received consulting fees from GSK, AstraZeneca, Novartis, Roche, Eli Lilly S.A., Pfizer, Genomic Health, Merck MSD, Novartis, PharmaMar, Tesaro, Advisory Boards: GSK, AstraZeneca, Novartis, Roche, Eli Lilly S.A., Pfizer, Genomic Health, Merck MSD, Novartis, PharmaMar, Tesaro Travel Support: GSK, AstraZeneca, Roche.

KJD: Travel grant from Roche Pharmaceutical.

KN: Supported by AACR-AstraZeneca Ovarian Cancer Research Fellowship.

FG: Supported by Swiss cancer Research foundation.

All other authors indicate no financial relationships.

Author Contributions

FG, NM, AB, FDS, MV, KJD contributed to the study conception and design. Material preparation, data collection and analysis were performed by FG, NM, AB, AS, TAZ, FDS. The first draft of the manuscript was written by FG all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Data Availability

The datasets in this study can be available from the corresponding author upon reasonable request.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval was obtained by the local Ethical Committee of Nordwest-und Zentralschweiz (EKNZ, BASEC 2021-01148). The anonymization of personal data was guaranteed.

seer.cancer.gov (accessed February 2023)
Durbecq V, Ameye L, Veys I, Paesmans M, Desmedt C, Sirtaine N, et al. A significant proportion of elderly patients develop hormone-dependant “luminal-B” tumours associated with aggressive characteristics. Crit Rev Oncol Hematol 2008;67:80–92. https://doi.org/10.1016/j.critrevonc.2007.12.008.
Engels CC, Kiderlen M, Bastiaannet E, van Eijk R, Mooyaart A, Smit VTHBM, et al. The clinical value of HER-2 overexpression and PIK3CA mutations in the older breast cancer population: a FOCUS study analysis. Breast Cancer Res Treat 2016;156:361–70. https://doi.org/10.1007/s10549-016-3734-y.
Bergen ES, Tichy C, Berghoff AS, Rudas M, Dubsky P, Bago-Horvath Z, et al. Prognostic impact of breast cancer subtypes in elderly patients. Breast Cancer Res Treat 2016;157:91–9. https://doi.org/10.1007/s10549-016-3787-y.
Yamada A, Kumamaru H, Shimizu C, Taira N, Nakayama K, Miyashita M, et al. Systemic therapy and prognosis of older patients with stage II/III breast cancer: A large-scale analysis of the Japanese Breast Cancer Registry. Eur J Cancer 2021;154:157–66. https://doi.org/10.1016/j.ejca.2021.06.006.
Fietz T, Zahn M-O, Köhler A, Engel E, Frank M, Kruggel L, et al. Routine treatment and outcome of breast cancer in younger versus elderly patients: results from the SENORA project of the prospective German TMK cohort study. Breast Cancer Res Treat 2018;167:567–78. https://doi.org/10.1007/s10549-017-4534-8.
Daniels B, Kiely BE, Tang M, Tervonen H, Pearson S-A. Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003-2015). BMC Cancer 2019;19:909. https://doi.org/10.1186/s12885-019-6126-y.
Jolly TA, Williams GR, Bushan S, Pergolotti M, Nyrop KA, Jones EL, et al. Adjuvant treatment for older women with invasive breast cancer. Womens Health (Lond Engl) 2016;12:129–45; quiz 145. https://doi.org/10.2217/whe.15.92.
Brain E, Caillet P, de Glas N, Biganzoli L, Cheng K, Lago LD, et al. HER2-targeted treatment for older patients with breast cancer: An expert position paper from the International Society of Geriatric Oncology. J Geriatr Oncol 2019;10:1003–13. https://doi.org/10.1016/j.jgo.2019.06.004.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659–72. https://doi.org/10.1056/NEJMoa052306.
Perez EA, Romond EH, Suman VJ, Jeong J-H, Sledge G, Geyer CE, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014;32:3744–52. https://doi.org/10.1200/JCO.2014.55.5730.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673–84. https://doi.org/10.1056/NEJMoa052122.
Mustacchi G, Cazzaniga ME, Pronzato P, De Matteis A, Di Costanzo F, Floriani I, et al. Breast cancer in elderly women: a different reality? Results from the NORA study. Ann Oncol 2007;18:991–6. https://doi.org/10.1093/annonc/mdm063.
Calderon E, Webb C, Kosiorek HE, Richard J Gray MD, Cronin P, Anderson K, et al. Are we choosing wisely in elderly females with breast cancer? Am J Surg 2019;218:1229–33. https://doi.org/10.1016/j.amjsurg.2019.08.004.
Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, et al. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol 2020;38:3743–52. https://doi.org/10.1200/JCO.20.00184.
Battisti NML, Hatton MQ, Reed MWR, Herbert E, Morgan JL, Bradburn M, et al. Observational cohort study in older women with early breast cancer: Use of radiation therapy and impact on health-related quality of life and mortality. Radiother Oncol 2021;161:166–76. https://doi.org/10.1016/j.radonc.2021.06.021.
Biganzoli L, Battisti NML, Wildiers H, McCartney A, Colloca G, Kunkler IH, et al. Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG). Lancet Oncol 2021;22:e327–40. https://doi.org/10.1016/S1470-2045(20)30741-5.
Smith BD, Jiang J, McLaughlin SS, Hurria A, Smith GL, Giordano SH, et al. Improvement in breast cancer outcomes over time: are older women missing out? J Clin Oncol 2011;29:4647–53. https://doi.org/10.1200/JCO.2011.35.8408.
Bouchardy C, Rapiti E, Fioretta G, Laissue P, Neyroud-Caspar I, Schäfer P, et al. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 2003;21:3580–7. https://doi.org/10.1200/JCO.2003.02.046.
van de Water W, Kiderlen M, Bastiaannet E, Siesling S, Westendorp RGJ, van de Velde CJH, et al. External validity of a trial comprised of elderly patients with hormone receptor-positive breast cancer. J Natl Cancer Inst 2014;106:dju051. https://doi.org/10.1093/jnci/dju051.
Mantarro S, Rossi M, Bonifazi M, D’Amico R, Blandizzi C, La Vecchia C, et al. Risk of severe cardiotoxicity following treatment with trastuzumab: a meta-analysis of randomized and cohort studies of 29,000 women with breast cancer. Intern Emerg Med 2016;11:123–40. https://doi.org/10.1007/s11739-015-1362-x.
Dao D, Zemla T, Jatoi A, Freedman RA, Hurria A, Muss H, et al. Older-Patient-Specific Cancer Trials: A Pooled Analysis of 2,277 Patients (A151715). Oncologist 2019;24:e284–91. https://doi.org/10.1634/theoncologist.2018-0803.
Shrestha A, Martin C, Burton M, Walters S, Collins K, Wyld L. Quality of life versus length of life considerations in cancer patients: A systematic literature review. Psychooncology 2019;28:1367–80. https://doi.org/10.1002/pon.5054.
Morgan JL, Burton M, Collins K, Lifford KJ, Robinson TG, Cheung K-L, et al. The balance of clinician and patient input into treatment decision-making in older women with operable breast cancer. Psychooncology 2015;24:1761–6. https://doi.org/10.1002/pon.3853.
Stueber TN, Diessner J, Bartmann C, Leinert E, Janni W, Herr D, et al. Effect of adjuvant radiotherapy in elderly patients with breast cancer. PLoS ONE 2020;15:e0229518. https://doi.org/10.1371/journal.pone.0229518.
Bagegni NA, Peterson LL. Age-related disparities in older women with breast cancer. Adv Cancer Res 2020;146:23–56. https://doi.org/10.1016/bs.acr.2020.01.003.
Freytag M, Herrlinger U, Hauser S, Bauernfeind FG, Gonzalez-Carmona MA, Landsberg J, et al. Higher number of multidisciplinary tumor board meetings per case leads to improved clinical outcome. BMC Cancer 2020;20:355. https://doi.org/10.1186/s12885-020-06809-1.
Keating NL, Landrum MB, Lamont EB, Bozeman SR, Shulman LN, McNeil BJ. Tumor boards and the quality of cancer care. J Natl Cancer Inst 2013;105:113–21. https://doi.org/10.1093/jnci/djs502.
El Saghir NS, Keating NL, Carlson RW, Khoury KE, Fallowfield L. Tumor boards: optimizing the structure and improving efficiency of multidisciplinary management of patients with cancer worldwide. Am Soc Clin Oncol Educ Book 2014:e461-6. https://doi.org/10.14694/EdBook_AM.2014.34.e461.
Bridges J, Hughes J, Farrington N, Richardson A. Cancer treatment decision-making processes for older patients with complex needs: a qualitative study. BMJ Open 2015;5:e009674. https://doi.org/10.1136/bmjopen-2015-009674.
Rollet Q, Bouvier V, Moutel G, Launay L, Bignon A-L, Bouhier-Leporrier K, et al. Multidisciplinary team meetings: are all patients presented and does it impact quality of care and survival - a registry-based study. BMC Health Serv Res 2021;21:1032. https://doi.org/10.1186/s12913-021-07022-x.
Bolle S, Smets EMA, Hamaker ME, Loos EF, van Weert JCM. Medical decision making for older patients during multidisciplinary oncology team meetings. J Geriatr Oncol 2019;10:74–83. https://doi.org/10.1016/j.jgo.2018.07.016.
Hahlweg P, Hoffmann J, Härter M, Frosch DL, Elwyn G, Scholl I. In absentia: an exploratory study of how patients are considered in multidisciplinary cancer team meetings. PLoS ONE 2015;10:e0139921. https://doi.org/10.1371/journal.pone.0139921.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–83. https://doi.org/10.1016/0021-9681(87)90171-8.
Yang X, Huang J, Zhu X, Shen K, Zhu J, Chen X. Compliance with multidisciplinary team recommendations and disease outcomes in early breast cancer patients: An analysis of 4501 consecutive patients. Breast 2020;52:135–45. https://doi.org/10.1016/j.breast.2020.05.008.
Ring A, Harder H, Langridge C, Ballinger RS, Fallowfield LJ. Adjuvant chemotherapy in elderly women with breast cancer (AChEW): an observational study identifying MDT perceptions and barriers to decision making. Ann Oncol 2013;24:1211–9. https://doi.org/10.1093/annonc/mds642.
Pons-Tostivint E, Daubisse-Marliac L, Grosclaude P, Oum Sack E, Goddard J, Morel C, et al. Multidisciplinary team meeting and EUSOMA quality indicators in breast cancer care: A French regional multicenter study. Breast 2019;46:170–7. https://doi.org/10.1016/j.breast.2019.06.001.
Rajan S, Foreman J, Wallis MG, Caldas C, Britton P. Multidisciplinary decisions in breast cancer: does the patient receive what the team has recommended? Br J Cancer 2013;108:2442–7. https://doi.org/10.1038/bjc.2013.267.
English R, Metcalfe C, Day J, Rayter Z, Blazeby JM, breast cancer multi-disciplinary team. A prospective analysis of implementation of multi-disciplinary team decisions in breast cancer. Breast J 2012;18:459–63. https://doi.org/10.1111/j.1524-4741.2012.01270.x.
Wyld L, Reed MWR, Collins K, Burton M, Lifford K, Edwards A, et al. Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices. Br J Surg 2021;108:499–510. https://doi.org/10.1093/bjs/znab005.
Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen MLG, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 2014;32:2595–603. https://doi.org/10.1200/JCO.2013.54.8347.
Mohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol 2018;36:2326–47. https://doi.org/10.1200/JCO.2018.78.8687.
Decoster L, Van Puyvelde K, Mohile S, Wedding U, Basso U, Colloca G, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†. Ann Oncol 2015;26:288–300. https://doi.org/10.1093/annonc/mdu210.
Hamaker ME, Jonker JM, de Rooij SE, Vos AG, Smorenburg CH, van Munster BC. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review. Lancet Oncol 2012;13:e437-44. https://doi.org/10.1016/S1470-2045(12)70259-0.
van de Water W, Bastiaannet E, Hille ETM, Meershoek-Klein Kranenbarg EM, Putter H, Seynaeve CM, et al. Age-specific nonpersistence of endocrine therapy in postmenopausal patients diagnosed with hormone receptor-positive breast cancer: a TEAM study analysis. Oncologist 2012;17:55–63. https://doi.org/10.1634/theoncologist.2011-0037.
Wyld L, Reed MW, Collins K, Ward S, Holmes G, Morgan J, et al. Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT. Southampton (UK): National Institute for Health and Care Research; 2022. https://doi.org/10.3310/XZOE2552.
Battisti NML, Andres MS, Lee KA, Ramalingam S, Nash T, Mappouridou S, et al. Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer. Breast Cancer Res Treat 2021;188:149–63. https://doi.org/10.1007/s10549-021-06192-w.
Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol 2008;26:1231–8. https://doi.org/10.1200/JCO.2007.13.5467.
Tan-Chiu E, Yothers G, Romond E, Geyer CE, Ewer M, Keefe D, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol 2005;23:7811–9. https://doi.org/10.1200/JCO.2005.02.4091.
Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE, Swain SM, et al. Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2. J Clin Oncol 2017;35:3942–8. https://doi.org/10.1200/JCO.2017.74.1165.
Romond EH, Jeong J-H, Rastogi P, Swain SM, Geyer CE, Ewer MS, et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2012;30:3792–9. https://doi.org/10.1200/JCO.2011.40.0010.
Advani PP, Ballman KV, Dockter TJ, Colon-Otero G, Perez EA. Long-Term Cardiac Safety Analysis of NCCTG N9831 (Alliance) Adjuvant Trastuzumab Trial. J Clin Oncol 2016;34:581–7. https://doi.org/10.1200/JCO.2015.61.8413.
Reeder-Hayes KE, Meyer AM, Hinton SP, Meng K, Carey LA, Dusetzina SB. Comparative Toxicity and Effectiveness of Trastuzumab-Based Chemotherapy Regimens in Older Women With Early-Stage Breast Cancer. J Clin Oncol 2017;35:3298–305. https://doi.org/10.1200/JCO.2016.71.4345.
de Azambuja E, Procter MJ, van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J, et al. Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01). J Clin Oncol 2014;32:2159–65. https://doi.org/10.1200/JCO.2013.53.9288.
Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 2017;389:1195–205. https://doi.org/10.1016/S0140-6736(16)32616-2.
Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: american society of clinical oncology clinical practice guideline. J Clin Oncol 2017;35:893–911. https://doi.org/10.1200/JCO.2016.70.5400.
Jawa Z, Perez RM, Garlie L, Singh M, Qamar R, Khandheria BK, et al. Risk factors of trastuzumab-induced cardiotoxicity in breast cancer: A meta-analysis. Medicine (Baltimore) 2016;95:e5195. https://doi.org/10.1097/MD.0000000000005195.
Bouwer NI, Jager A, Liesting C, Kofflard MJM, Brugts JJ, Kitzen JJEM, et al. Cardiac monitoring in HER2-positive patients on trastuzumab treatment: A review and implications for clinical practice. Breast 2020;52:33–44. https://doi.org/10.1016/j.breast.2020.04.005.
Huang P, Huang J-H, Zheng Y-B, Cao W-M, Shao X-Y, Chen J-Q, et al. Cardiac Safety in Breast Cancer Patients Receiving Pegylated Liposome Doxorubicin Sequential Anti-HER2 Monoclonal Antibody Therapy. Front Pharmacol 2022;13:883600. https://doi.org/10.3389/fphar.2022.883600.
McArthur HL, Chia S. Cardiotoxicity of trastuzumab in clinical practice. N Engl J Med 2007;357:94–5. https://doi.org/10.1056/NEJMc070065.
Dent S, Fergusson D, Aseyev O, Stober C, Pond G, Awan AA, et al. A Randomized Trial Comparing 3- versus 4-Monthly Cardiac Monitoring in Patients Receiving Trastuzumab-Based Chemotherapy for Early Breast Cancer. Curr Oncol 2021;28:5073–83. https://doi.org/10.3390/curroncol28060427.
Pituskin E, Mackey JR, Koshman S, Jassal D, Pitz M, Haykowsky MJ, et al. Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101-Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity. J Clin Oncol 2017;35:870–7. https://doi.org/10.1200/JCO.2016.68.7830.
Calvillo-Argüelles O, Abdel-Qadir H, Michalowska M, Billia F, Suntheralingam S, Amir E, et al. Cardioprotective Effect of Statins in Patients With HER2-Positive Breast Cancer Receiving Trastuzumab Therapy. Can J Cardiol 2019;35:153–9. https://doi.org/10.1016/j.cjca.2018.11.028.
Livi L, Barletta G, Martella F, Saieva C, Desideri I, Bacci C, et al. Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial. JAMA Oncol 2021;7:1544–9. https://doi.org/10.1001/jamaoncol.2021.3395.
Iyer NG, Chua MLK. Multidisciplinary team meetings - challenges of implementation science. Nat Rev Clin Oncol 2019;16:205–6. https://doi.org/10.1038/s41571-018-0148-2.
Bortot L, Targato G, Noto C, Giavarra M, Palmero L, Zara D, et al. Multidisciplinary team meeting proposal and final therapeutic choice in early breast cancer: is there an agreement? Front Oncol 2022;12:885992. https://doi.org/10.3389/fonc.2022.885992.

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Adherence to multidisciplinary team meeting recommendations in elderly patients with HER2-positive breast cancer

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Adherence to MDTM recommendations

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