Die Therapieplanung junger Frauen mit Mammakarzinom – eine besondere Herausforderung

Zusammenfassung

Patientinnen unter 40 Jahren werden allein aufgrund ihres Alters oft unabhängig von der vorhandenen Tumorbiologie als Hochrisikogruppe betrachtet und einer aggressiven Therapie zugeführt. Diese Patientinnengruppe befindet sich jedoch in einer speziellen Lebensphase, in der Über- und Untertherapie sowie unnötige Behandlungen strikt zu vermeiden sind. Die Wahl eines falschen oder zu aggressiven Chemotherapie-Regimes kann bei Frauen im reproduktiven Alter zur eingeschränkten Ovarialfunktion oder gar dem Verlust der Fertilität führen. Dieses und andere spezifische Themen sollten bei der Therapieplanung junger Mammakarzinompatientinnen interdisziplinär mit Gynäkologen, Onkologen und Strahlentherapeuten diskutiert werden. Das frühe Auftreten der Erkrankung bei Patientinnen in einer speziellen Lebenssituation stellt das Team insbesondere bei der Wahl des richtigen Therapiekonzepts oftmals vor eine Herausforderung.

Kernaussagen:

• Die zugrundeliegende Tumorbiologie bedingt das Risiko.

• Die Indikation zu einer leitliniengerechte Standardtherapie ist obligat.

• Die besondere Lebenssituation erfordert die Berücksichtigung wichtiger Themen vor Therapiebeginn: Kinderwunsch, ggf. bestehende Schwangerschaft, Abklärung familiärer Belastungen, Risikoberatung bei < 35 Jahren, Abwägung Wirksamkeit der Therapie vs. Langzeit-Toxizitäten, Verhütung

• Junge Patientinnen benötigen obligat ein im interdisziplinären Tumorboard festgelegtes Therapiekonzept.

• Nicht alle prognostischen Tests sind für junge Frauen einsetzbar.

• Es besteht keine Indikation zur prophylaktischen Gabe von Bisphosphonaten.

Abstract

Due to their young age, patients under the age of forty are considered as a high-risk group independent from the existing tumor biology. Therefore, this group of patients often undergoes more aggressive treatment concepts. However, the special phase of life of young patients should prohibit over- or under-therapy and unnecessary treatments are to be strictly avoided. For women in reproductive age, the choice of wrong or too aggressive chemotherapy regimens can result in restricted ovarian function or even loss of fertility. With respect to the individual situation of the patient, specific issues should be discussed involving an interdisciplinary board of gynecologists, oncologists and radiotherapists. The early appearance of the disease in patients with individual living conditions often represents a challenge for the involved team.

Schlüsselwörter

Mammakarzinom, - junge Patientin - Risiko - Chemotherapie - Gentests - Biomarker

Key words

breast cancer - young patient - risk - chemotherapy - genetic testing - biomarkers

• Referenzen

• 1 Robert Koch-Institut. Krebs in Deutschland – Häufigkeiten und Trends. 2012
• 2 Samphao S, Wheeler AJ, Rafferty E et al. Diagnosis of breast cancer in women age 40 and younger: delays in diagnosis result from underuse of genetic testing and breast imaging. Am J Surg 2009; 198 (04) 538-543
• 3 Engel J. Tumorregister München. 2012
• 4 Cuzick J, Ambroisine L, Davidson N et al. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 2007; 369 (9574) 1711-1723
• 5 Brown LM, Chen BE, Pfeiffer RM et al. Risk of second non-hematological malignancies among 376,825 breast cancer survivors. Breast Cancer Res Treat 2007; 106 (03) 439-451
• 6 Kroman N, Jensen MB, Wohlfahrt J et al. Factors influencing the effect of age on prognosis in breast cancer: population based study. BMJ 2000; 320 (7233) 474-478
• 7 Cardoso F, Loibl S, Pagani O et al. The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer. Eur J Cancer 2012; 48: 3355-3377
• 8 Houlston RS, Peto J. The search for low-penetrance cancer susceptibility alleles. Oncogene 2004; 23 (38) 6471-6476
• 9 Antoniou A, Pharoah PD, Narod S et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003; 72 (05) 1117-1130
• 10 Kreienberg R. Interdisziplinäre S3-Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. Zuckschwerdtverlag; 2012
• 11 Schover LR, Rybicki LA, Martin BA et al. A pilot survey of survivors' attitudes and experiences. Cancer 1999; 86 (04) 697-709
• 12 Valachis A, Tsali L, Pesce LL et al. Safety of pregnancy after primary breast carcinoma in young women: a meta-analysis to overcome bias of healthy mother effect studies. Obstet Gynecol Surv 2010; 65: 786-793
• 13 Peate M, Meiser B, Hickey M et al. The fertility-related concerns, needs and preferences of younger women with breast cancer: a systematic review. Breast Cancer Res Treat 2009; 116 (02) 215-223
• 14 Thewes B, Meiser B, Duric VM et al. What survival benefits do premenopausal patients with early breast cancer need to make endocrine therapy worthwhile?. Lancet Oncol 2005; 6 (08) 581-588
• 15 Stearns V, Beebe KL, Iyengar M et al. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 2003; 289 (21) 2827-2834
• 16 Loibl S, Schwedler K, Von Minckwitz G et al. Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients--a double-blind, randomized study. Ann Oncol 2007; 18 (04) 689-693
• 17 Hickey M, Peate M, Saunders CM et al. Breast cancer in young women and its impact on reproductive function. Hum Reprod Update 2009; 15 (03) 323-339
• 18 Partridge AH, Ruddy KJ, Gelber S et al. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril 2010; 94: 638-644
• 19 Lee S, Ozkavukcu S, Heytens E et al. Value of early referral to fertility preservation in young women with breast cancer. J Clin Oncol 2010; 28: 4683-4686
• 20 Pecking AP. Evaluation by lymphoscintigraphy of the effect of a micronized flavonoid fraction (Daflon 500 mg) in the treatment of upper limb lymphedema. Int Angiol 1995; 14 (03) (Suppl. 01) 39-43
• 21 Letourneau JM, Melisko ME, Cedars MI et al. A changing perspective: improving access to fertility preservation. Nat Rev Clin Oncol 8 (01) 56-60
• 22 Davies C, Godwin J, Gray R et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771-784
• 23 Fisher B, Jeong JH, Bryant J et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet 2004; 364: 858-868
• 24 Early Breast Cancer Trialists Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687-1717
• 25 Huober J, Von Minckwitz G, Denkert C et al. Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat 124 (01) 133-140
• 26 Swain SM, Jeong JH, Geyer CE et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 362 (22) 2053-2065
• 27 Citron ML, Berry DA, Cirrincione C et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003; 21 (08) 1431-1439
• 28 Martin M, Pienkowski T, Mackey J et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005; 352 (22) 2302-2313
• 29 Clarke M, Collins R, Darby S et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366 (9503) 2087-2106
• 30 Clarke M, Coates AS, Darby SC et al. Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet 2008; 371 (9606) 29-40
• 31 Webseite: 2013 www.ago-online.org
• 32 Aapro MS, Bohlius J, Cameron DA et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011; 47: 8-32
• 33 Untch M, Gelber RD, Jackisch C et al. Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol 2008; 19 (06) 1090-1096
• 34 Smith I, Procter M, Gelber RD et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369 (9555) 29-36
• 35 Beadle BM, Woodward WA, Buchholz TA. The impact of age on outcome in early-stage breast cancer. Semin Radiat Oncol 2011; 21: 26-34
• 36 Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet 2000; 355 (9217) 1757-1770
• 37 Kunkler IH, Canney P, Van Tienhoven G et al. Elucidating the role of chest wall irradiation in 'intermediate-risk' breast cancer: the MRC/EORTC SUPREMO trial. Clin Oncol (R Coll Radiol) 2008; 20 (01) 31-34
• 38 Paik S, Tang G, Shak S et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006; 24 (23) 3726-3734
• 39 Gnant M, Mlineritsch B, Stoeger H et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol 2011; 12: 631-641
• 40 Gnant M. Zoledronic acid in the treatment of early-stage breast cancer: is there a final verdict?. Curr Oncol Rep 14 (01) 35-43