Abstract
Purpose
This study aims to answer the questions where breast cancer patients in Germany receive follow-up care (with what types of doctors) and what are the long-term problems and treatment regrets of breast cancer patients.
Methods
In the prospective multicenter cohort study BRENDA II (“Breast Cancer under Evidence-Based Guidelines”), 456 patients with primary breast cancer were sampled consecutively over a period of 4 years (2009–2012) and contacted again 5 years after surgery. Long-term problems were elicited on a 4-point Likert scale ranging from 0 (‘not at all’) to 3 (‘very much’).
Results
82% of the patients receive follow-up (FU) at the private practice gynecologist. In 22%, the initial treating hospital is involved in the FU, and in 20% the general practitioner does this (multiple answers possible). Long-term problems attributed to the treatment were most often related to endocrine therapy (mean 1.29) and to chemotherapy (mean 0.94).
Most of the patients were happy to have had radiotherapy (95%). For chemotherapy, endocrine therapy, and antibody therapy, the satisfaction for the treatment decision was 87%, 87%, and 84% respectively. Among patients who reported they regretted having undergone a recommended treatment, it was most often for endocrine therapy (5%) and chemotherapy (4%).
Conclusion
In Germany, different specialists are involved in the patients’ FU care for BC. The detection of long-term problems due to BC treatment is an essential part of FU care.
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Introduction
Breast cancer (BC) is the most frequent cancer among women [1]. Due to early detection of BC and improvements in the available treatment strategies, more than 80% of the patients will be long-term survivors [2,3,4]. After curative BC treatment, patients move on to follow-up care, which marks the shift from curative care to survivorship. FU in BC care involves periodic visits for history and physical examination and annual surveillance mammograms [5, 6]. Detection of recurrent and new primary BC is the main goal of the FU program [7, 8].
In Germany, BC is commonly treated by a gynecologic oncologist, and, hence, they are usually involved in the patient's FU care. However, general practitioners, medical oncologist, radio-oncologist, or other doctors also perform FU care for BC. To date, it is not known to which doctors BC patients go for FU care and to what extent. Thus, this paper addresses the question as to where (to a private practice or hospital) and from what types of doctors patients receive FU care. Moreover, we were interested in whether there are differences between patients with and without metastatic disease.
Besides monitoring for cancer recurrence, the objectives of FU care also include the improvement of quality of life and physical performance as well as the reduction of therapy-related side effects. Identifying long-term problems and the patient's opinions related to the different treatment strategies of the adjuvant setting such as surgery, chemotherapy, radiotherapy, endocrine therapy, and antibody therapy are essential for example to understand treatment discontinuation that prevents patients from undergoing guideline-adherent adjuvant treatment in primary BC care [9, 10]. Therefore, the aim of the prospective BRENDA II study is to assess these patient-related factors to promote guideline adherence, which may be associated with improved survival parameters in BC.
This study aims to answer the following questions:
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1.
Where do patients receive FU care (with what types of doctors)? Are there differences between patients who have metastases and those that do not?
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2.
What are the patients’ current complaints related to the treatment they have received?
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3.
In hindsight, what are the patients’ attitudes regarding the treatment they have received?
Methods
Data collection
In the prospective multicenter cohort study BRENDA II (“Breast Cancer under Evidence-Based Guidelines”), patients with primary BC were sampled consecutively over a period of 4 years (2009–2012). Patients were approached before surgery (t1), before initiation of adjuvant treatment (t2), after completion of adjuvant radio- and/or chemotherapy (t3), and contacted again 5 years after surgery (t4). Patients were eligible for this study if they had been diagnosed with primary histologically confirmed BC. Exclusion criteria were: metastatic or recurrent disease at baseline, bilateral BC, primary occult disease and phylloides tumor, inability to complete a questionnaire, and no written informed consent. Following a consultation, each patient was informed about the study by her doctor and asked to participate. If she agreed, the doctor handed over the first series of questionnaires and interviewed the patient. FU interviews were performed by trained study nurses. We collected data at the University Medical Center in Ulm, Kempten Hospital, Memmingen Hospital, and Esslingen Hospital, all of which are breast cancer centers certified by the German Cancer Society. Ethical approval was obtained from the Ethics Committee of Ulm University.
Instruments
Clinical data were obtained from the medical records by trained data managers. The patients' individual risk was defined according to the Nottingham Prognostic Index based on the size of the lesion, number of lymph nodes involved, and tumor grade and then consequently grouped into risk groups [11]. Missing values for any of the three parameters were imputed using the mean. The occurrence of distant metastases was reported by the patients at t4.
Socio-demographic data such as age, marital status, and employment were provided by the patient.
We elicited long-term problems by asking: ‘If there are any current problems, how much are they, in your opinion, related to the following treatments: breast surgery, axillary lymph node dissection, radiotherapy, chemotherapy, endocrine therapy, antibody therapy?’ Responses were collected on a 4-point Likert scale ranging from 0 (‘not at all’) to 3 (‘very much’). Patients could also tick ‘I did not receive this treatment’. Potential treatment regrets were elicited by asking ‘Are you happy/sorry about having done radiotherapy/chemotherapy/endocrine therapy/antibody therapy?’ and accordingly ‘Are you happy/sorry about having refused to do radiotherapy/chemotherapy/endocrine therapy/antibody therapy?’
Statistical analysis
Absolute and relative frequencies were calculated for categorical variables and mean scores for continuous variables to describe the sample. Non-participants at t4 were compared to participants regarding age at baseline and risk group (according to Nottingham Prognostic Index) using analysis of variance and Chi2 tests.
We defined the proportion of patients in the various types of FU care (the kind of doctor the participants are receiving FU care from) and compared the patients with and without metastases and in different educational groups using 2 × k tables and Chi2 tests.
Statistical analyses were performed using STATA 12.1 (StataCorp LP, College Station, TX, USA).
Results
Sample
857 patients with primary BC were treated at the collaborating clinics during the study enrollment period and 759 patients participated in the BRENDA II study. At t4, 456 (60%) patients participated again, and these data were used for analysis. 101 (13%) other patients declined (51 of them had participated at t3 but declined now at t4, the remaining 50 had already declined before t4 during the course of the study), 60 (8%) were known to be deceased, 1 had moved to an unknown address abroad, and 141 (19%) did not reply for unknown reasons.
The participants were on average 63 years old at t4 (SD 11, minimum 31, maximum 93 years). They were at baseline on average younger than those who declined (+ 7 years) and those who were deceased (+ 8 years). Patients with an unknown reason for non-participation had the same age as the participants. Also, the participants had a better prognostic outlook at baseline according to the Nottingham Prognostic Index than those who were deceased at t4 (p < 0.001).
Baseline clinical and socio-demographic data are displayed in Tables 1 and 2.
Treatment
All patients received surgical care, 86% breast-conserving surgery, and 14% mastectomy (Table 2). 31% of the patients received axillary lymph node dissection. The time since surgery was on average 5.5 years (median 5.3, minimum 4.3, maximum 7.3 years). 46% of the patients were treated with chemotherapy, and 12% with additional antibody therapy. The majority of the patients received adjuvant radiotherapy (91%) and endocrine therapy (82%). Regarding the type of endocrine therapy, more than half of the patients (55%) were exposed to tamoxifen, and 59% of the patients were treated with some type of aromatase inhibitor (Table 3).
Follow-up care
In the majority of the patients, the private practice gynecologist performs their FU care (82%) (Table 4). In 22%, the initial treating hospital is involved in the FU, and in 20% the general practitioner (GP) does this. Other hospitals, private practice medical oncologists, private practice radio-oncologist, or others are rarely consulted for FU care. Fifteen of the patients reported they did not attend any doctor for FU care.
13 patients had distant metastases at t4, and they visited at least one doctor for FU care. In the metastatic setting, patients go less often to a private practice gynecologist (p = 0.007) and more often to a private practice medical oncologist (p = 0.06) compared to patients without distant metastases. No statistically significant differences were found for FU care in the initial treating hospital, with the GP, or in a private practice radio-oncologist. There was no evidence for an effect of education on which doctor was visited for FU care (Table 4).
Long-term problems
Long-term problems attributed to the treatment by the patients were most often related to endocrine therapy (mean 1.29) and to chemotherapy (mean 0.94). Thereafter, problems are associated with surgery (axillary lymph node dissection > surgery of the breast). Rarely, patients report long-term problems due to radiation therapy (0.54) or antibody therapy (0.28) (Fig. 1).
Treatment regret
In general, many patients were happy to have had the curative treatment possibilities listed in Table 5a. In 41% of patients, chemotherapy was not recommended, and in 19% endocrine therapy was not recommended. Regarding only those patients who had had a doctor's recommendation for a particular therapy (Table 5b), most of the patients were happy to have had radiotherapy (95%). For chemotherapy, endocrine therapy, and antibody therapy, the satisfaction for the treatment decision was 87%, 87%, and 84% respectively. Among patients who reported they regretted having undergone a recommended treatment, it was in descending order for endocrine therapy (5%), chemotherapy (4%), radiotherapy (3%), and antibody therapy (1%).
On the other hand, patients almost never regretted having refused a recommended treatment. Among patients who indicated they were happy they had decided against a treatment recommendation, it was most often for antibody therapy (13%), followed by chemotherapy (10%), endocrine therapy (8%), and radiotherapy (2%).
Discussion
Based on BC statistics, there are millions of women alive who have been diagnosed with BC in the past [12]. A steady increase in this number underlines the importance of FU care to provide optimal treatment and improve BC outcomes. In Germany, different specialized doctors such as gynecologists (in private practice or hospital), medical oncologist, or radio-oncologist are involved in the patient's FU care. Thus, it would also be important that clinical cancer registries document where patients receive their FU. To ensure standardized FU, national guidelines are well established [6, 7]. Therefore, in Germany, several specialists of each sector are also members of the national guideline panels for BC. On the other hand, a considerable number of patients receive FU at their GP, which is confirmed by our data. GPs are well positioned to provide cancer care FU because of their knowledge of the personal history, social background, and comorbidities of the patients [13, 14]. BC is the most common cancer in women, and many GPs will have several BC patients in their practice who are currently undergoing treatment or were affected in the past. Furthermore, as many BC patients are elderly, FU care and the management of comorbidities is becoming increasingly essential [15]. As previous studies have demonstrated, FU care for BC patients provided by their GP is a safe and acceptable alternative to specialist FU care [16]. In our study cohort, the GP was even more involved in the patient's care if she had metastatic disease. Previous studies confirm that the GP also plays an important role in palliative care for cancer patients [17].
In addition to detecting recurrent BC, a main goal of FU is the management of treatment-related side effects and the improvement of quality of life. Thus, the prospective BRENDA study sets out to better understand BC patients’ long-term problems and treatment regrets. We found that patients in the BRENDA study in general did not report a high level of long-term problems. Indeed, the risk of serious side effects in early stage BC treatment is small [18]. In the BRENDA cohort, patients’ current complaints were most often related to endocrine therapy, and, for the patients who regretted having undergone a certain treatment, it was most often concerning endocrine therapy. This underlines the importance in daily clinical practice to detect current problems and to provide supportive care especially for the long treatment period of endocrine treatment. Surprisingly, in our cohort, chemotherapy is reported only in second position regarding long-term problems or treatment regrets. This is contrary to other studies which have demonstrated that chemotherapy is often associated with decreased quality of life, both short and long term [19,20,21]. On the other hand, the data for this analyses were collected at t4, which is on average 5 years after surgery. Hence, the majority of the patients who had a recommendation for endocrine therapy are still undergoing this treatment because most patients start it after radiation [22] and especially because extended adjuvant endocrine treatment is nowadays standard in high-risk primary BC [23, 24]. Therefore, current problems due to endocrine therapy are more present to the patient than chemotherapy-related problems, as chemotherapy lays further back in time. Furthermore, patients participating in the BRENDA II study were younger than patients who declined. As was demonstrated in a previous study, younger age was associated with a more negative perception of endocrine treatment, presumably because side effects are more detrimental for premenopausal women [19].
After long-term problems caused by endocrine treatment and chemotherapy, patients reported long-term problems associated with surgery, especially axillary lymph node dissection. Patients who had axillary lymph node dissection have a higher rate of morbidity, mainly caused by lymphedema compared to patients with sentinel node biopsy alone [25]. Furthermore, lymphedema of the arm presents one of the most important long-term sources of distress following surgery for BC [26]. This underlines the significance of the lower radicalness in axillary surgery in recent times also from the patient’s point of view [27, 28]. There were rarely long-term problems and treatment regrets concerning radiotherapy. Nowadays, due to modern radio-oncology techniques, the side effects of radiotherapy have been considerably reduced [29, 30]. This has translated into decreased fear toward radiotherapy [19] and to a basically positive perception in our study cohort.
In the BRENDA cohort, 12% of the patients received antibody therapy, in particular trastuzumab, which was the standard in Her2-positive primary BC in combination with adjuvant chemotherapy at the time [31,32,33]. Patients in the BRENDA cohort rarely associated long-term problems with antibody therapy, and there were almost no patients with treatment regrets toward antibody therapy. Thus, our findings underline the results of previous trials which have demonstrated a good tolerance to adjuvant trastuzumab [34, 35]. On the other hand, 13% of the patients in the BRENDA cohort indicated they were happy to have refused a recommended antibody therapy. It is very likely that patients of this group overestimated the side effects of trastuzumab.
While interpreting the results of our study, its limitations should be taken into account.
First, the extent to which patients discontinued their treatment because of side effects or long-term problems was not analyzed. Thus, we can only assume that a higher level of long-term problems might cause treatment discontinuation and accordingly guideline violation in BC treatment. Because of the short follow-up in the BRENDA II study, we cannot demonstrate outcome results, but there is retrospective evidence from the BRENDA I study demonstrating that non-adherence to guidelines is associated with worse outcome parameters [10]. Further limitations are that problems and treatment regrets were only evaluated at one time point 5 years after surgery, due to limited financial resources; whether the patients who indicated problems concerning endocrine therapy have already finished their treatment or are still undergoing endocrine treatment was also not evaluated. A longer follow-up period or an evaluation at several time points would be interesting, as the results concerning long-term problems and treatment regrets may further change over time.
In conclusion, this study shows that, in Germany, different specialist are involved in the patients’ FU care for BC. This underlines the importance of national guidelines to ensure standardized treatment. The detection of long-term problems due to BC treatment is an essential part of FU care. Further studies are required to analyze the effect of long-term problems and treatment regrets on treatment discontinuation and consequently on BC outcomes.
References
https://www.cancer.net/cancer-types/breast-cancer/statistics. Accessed 25 Nov 2018
Van Ewijk R, Schwentner L, Wöckel A (2013) Trends in patient characteristics, treatment and survival in breast cancer in a non-selected retrospective clinical cohort study of 2,600 patients. Arch Gynecol Obstet 287(1):103–110
Van Luijt PA, Fracheboud J, Heijnsdijk EA, National evaluation team for breast cancer screening in Netherlands study groups (NETB) (2013) Nation-wide data on screening performance during the transition to digital mammography: observations in 6 million screens. Eur J Cancer 49(16):3517–3525
Wo JY, Chen K, Neville BA (2011) Effect of very small tumor size on cancer-specific mortality in node-positive breast cancer. J Clin Oncol 29(19):2619–2627
Khatcheressian JL, Hurley P, Bantug E et al (2013) Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 31(7):961–965
Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.1,2018 AWMF Registernummer: 032-045OL. https://www.leitlinienprogramm-onkologie.de/leitlinien/mammakarzinom/ (abgerufen am: 13.09.2018)
https://www.nccn.org/patients/guidelines/stage_i_ii_breast/files/assets/common/downloads/files/stageibreast.pdf. Accessed 25 Nov 2018
Schwentner L, Van Ewijk R, Kurzeder C, Hoffmann I, König J, Kreienberg R, Blettner M, Wöckel A (2013) Participation in adjuvant clinical breast cancer trials: does study participation improve survival compared to guideline adherent adjuvant treatment? A retrospective multi-centre cohort study of 9,433 patients. Eur J Cancer 49(3):553–563
Hancke K, Denkinger MD, König J (2010) Standard treatment of female patients with breast cancer decreases substantially for women aged 70 years and older: a German clinical cohort study. Ann Oncol 21(4):748–753
Galea MH, Blamey RW, Elston CE (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22:207–219
https://www.wcrf.org/dietandcancer/cancer-trends/breast-cancer-statistics. Accessed 25 Nov 2018
Dahlhaus A, Vanneman N, Guethlin C (2014) German general practitioners’ views on their involvement and role in cancer care: a qualitative study. Fam Pract 31:209–214
Sisler J, Chaput G, Sussman J, Ozokwelu E (2016) Follow-up after treatment for breast cancer: practical guide to survivorship care for family physicians. Can Fam Physician 62:805–811
Leinert E, Singer S, Janni W (2017) The impact of age on quality of life in breast cancer patients receiving adjuvant chemotherapy: a comparative analysis from the prospective multicenter randomized ADEBAR trial. Clin Breast Cancer 17(2):100–106
Grunfeld E, Levine MN, Julian JA (2006) Randomized trial of long-term follow-up for early-stage breast cancer: a comparison of family physician versus specialist care. J Clin Oncol 24(6):848–855
Dahlhaus A, Vanneman N, Siebenhofer A (2013) Involvement of general practitioners in palliative cancer care: a qualitative study. Support Care Cancer 21(12):3293–3300
Tao JJ, Visvanathan K, Wolff AC (2015) Long term side effects of adjuvant chemotherapy in patients with early breast cancer. Breast (Edinburgh, Scotland) 24(02):S149–S153
Singer S, Blettner M, Kreienberg R (2015) Breast cancer patients' fear of treatment: results from the Multicenter Longitudinal Study BRENDA II. Breast Care (Basel) 10(2):95–100
Fernandes-Taylor S, Bloom JR (2011) Post-Treatment regret among young breast cancer survivors. Psycho-oncol 20(5):506–516
Akechi T, Okuyama T, Endo C (2010) Anticipatory nausea among ambulatory cancer patients undergoing chemotherapy: prevalence, associated factors, and impact on quality of life. Cancer Sci 101:2596–2600
Cecchini MJ, Yu E, Potvin K, D’souza D, Lock M (2015) Concurrent or sequential hormonal and radiation therapy in breast cancer: a literature review. Cureus 7(10):e364. https://doi.org/10.7759/cureus.364
Davies C, Pan H, Godwin J et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381(9869):805–816
Goss PE, Ingle JN, Pritchard KI et al (2016) Extending aromatase-inhibitor adjuvant therapy to 10 Years. N Engl J Med 375(3):209–219
DiSipio T, Rye S, Newman B, Hayes S (2013) Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and metaanalysis. Lancet Oncol 14:500–515
Kuehn T, Klauss W, Darsow M (2000) Long-term morbidity following axillary dissection in breast cancer patients—clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors. Breast Cancer Res Treat 64(3):275–286
Janni W, Kuehn T, Schwentner L et al (2014) Sentinel node biopsy and axillary dissection in breast cancer—the evidence and its limits. Dtsch Arztebl Int 111(14):244–249
Giuliano AE, McCall L, Beitsch P et al (2010) Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 252:426–432
Shaitelman SF, Schlembach PJ, Arzu I et al (2015) Acute and short-term toxic effects of conventionally fractionated vs hypofractionated whole-breast irradiation: a randomized clinical trial. JAMA Oncol 1:931–941
Whelan TJ, Pignol J, Levine MN et al (2010) Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 362:513–520
Piccart-Gebhart MJ, Procter M, Leyland-Jones B (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672
Romond EH, Perez EA, Bryant J (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684
Slamon D, Eiermann W, Robert N (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283
de Azambuja E, Procter MJ, van Veldhuisen DJ et al (2014) Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1–01). J Clin Oncol 32:2159–2165
Cameron D, Piccart-Gebhart MJ, Gelber RD (2017) 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 389(10075):1195–1205
Funding
This work was supported by the German Federal Ministry of Education and Research (BMBF-Grant-01ZP0505).
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EL: manuscript writing. RK: funding acquisition, conceptualization. AW: funding acquisition, conceptualization, data collection. TK: data collection. FF: data collection. RF: data collection. WJ: data collection. KT: manuscript writing. SS: conceptualization, methodology, manuscript writing. LS: conceptualization, manuscript writing.
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Susanne Singer has received a research grant from Pfizer, the quality of life prize from Lilly, travel grants from Genzyme, and lecture fees from Astra Zeneca, Pfizer, Bristol-Myers Squibb, and Boehringer Ingelheim. The other authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Leinert, E., Kreienberg, R., Wöckel, A. et al. Survivors of primary breast cancer 5 years after surgery: follow-up care, long-term problems, and treatment regrets. Results of the prospective BRENDA II-study. Arch Gynecol Obstet 301, 761–767 (2020). https://doi.org/10.1007/s00404-020-05437-1
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DOI: https://doi.org/10.1007/s00404-020-05437-1