Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast

Abstract

Background Invasive lobular carcinoma (ILC) comprises around 10 – 15% of invasive breast cancers. Few prior studies have demonstrated a unique pattern of metastases between ILC and the more common invasive ductal carcinoma (IDC). To our knowledge, such data is limited to first sites of distant recurrence. We aimed to perform a comparison of the metastatic pattern of ILC and IDC at first distant recurrence as well as over the entire course of metastatic disease.

Methods We used a prospectively collated database of patients with metastatic breast cancer. Breast cancer recurrence or metastases were classified into various sites and a descriptive analysis was performed.

Results Among 761 patients, 88 (11.6%) were diagnosed with ILC and 673 (88.4%) with IDC. Patients with ILC showed more frequent metastases to the bone (56.8 vs. 37.7%, p = 0.001) and gastrointestinal (GI) tract (5.7 vs. 0.3%, p < 0.001) as first site of distant recurrence, and less to organs such as lung (5.7 vs. 24.2%, p < 0.001) and liver (4.6 vs. 11.4%, p = 0.049). Over the entire course of metastatic disease, more patients with ILC had ovarian (5.7 vs. 2.1%, p = 0.042) and GI tract metastases (8.0 vs. 0.6%, p < 0.001), also demonstrating reduced tendency to metastasize to the liver (20.5 vs. 49.0%, p < 0.001) and lung (23.9 vs. 51.9%, p < 0.001). All associations but bone held after sensitivity analysis on hormonal status. Although patients presenting with ILC were noted to have more advanced stage at presentation, recurrence-free survival in these patients was increased (4.8 years vs. 3.2 years, p = 0.017). However, overall survival was not (2.5 vs. 2.0 years, p = 0.75).

Conclusion After accounting for hormone receptor status, patients with IDC had greater lung/pleura and liver involvement, while patients with ILC had a greater propensity to develop ovarian and GI metastases both at first site and overall. Clinicians can use this information to provide more directed screening for metastases; it also adds to the argument that these two variants of breast cancer should be managed as unique diseases.

Zusammenfassung

Einleitung Invasiv-lobuläre Karzinome (ILC) machen rund 10 – 15% aller invasiven Brustkrebserkrankungen aus. Einige frühere Studien haben gezeigt, dass das ILC und das häufiger anzutreffende invasiv-duktale Karzinom (IDC) jeweils eigene Metastasierungsmuster aufweisen. Soweit uns bekannt ist, beschränken sich diese Daten auf die Lokalisation der ersten Fernrezidive. Ziel dieser Studie war es, die Metastasierungsmuster von ILC und IDC bei den ersten Fernrezidiven sowie über den gesamten Verlauf der Metastasierung zu vergleichen.

Methoden Grundlage der Studie war eine prospektiv zusammengestellte Datenbank von Patientinnen mit metastasiertem Brustkrebs. Brustkrebsrezidive bzw. Metastasen wurden nach deren Lokalisation klassifiziert, und die Daten wurden einer deskriptiven Analyse unterzogen.

Ergebnisse Unter 761 Patientinnen wurde bei 88 (11,6%) die Diagnose ILC gestellt und bei 673 (88,4%) die Diagnose IDC. Bei Patientinnen mit ILC traten die ersten Fernrezidive häufiger in Form von Knochenmetastasen (56,8 vs. 37,7%, p = 0,001) und Metastasen des Magen-Darm-Trakts auf (5,7 vs. 0,3%, p < 0,001) und nicht in Organen wie Lunge (5,7 vs. 24,2%, p < 0,001) oder Leber (4,6 vs. 11,4%, p = 0,049). Über den gesamten Verlauf der metastatischen Erkrankung waren Ovarialkarzinome (5,7 vs. 2,1%, p = 0,042) und Metastasen des Magen-Darm-Trakts (8,0 vs. 0,6%, p < 0,001) häufiger bei Patientinnen mit ILC anzutreffen, wohingegen Metastasen in der Leber (20,5 vs. 49,0%, p < 0,001) und der Lunge (23,9 vs. 51,9%, p < 0,001) weniger häufig vorkamen. Nach Beachtung des Hormonstatus wurden alle Zusammenhänge außer Knochenmetastasen in der Sensitivitätsanalyse bestätigt. Obwohl das Erkrankungsstadium bei der Erstvorstellung von Patientinnen mit ILC fortgeschrittener war, hatten diese Patientinnen ein höheres rezidivfreies Überleben (4,8 Jahre vs. 3,2 Jahre, p = 0,017). Trotzdem hatten diese Patientinnen kein längeres Gesamtüberleben (2,5 vs. 2,0 Jahre, p = 0,75).

Schlussfolgerung Nach Berücksichtigung des Hormonrezeptorstatus wiesen Patientinnen mit IDC eher Metastasen in der Lunge/der Pleura und in der Leber auf, wohingegen Patientinnen mit ILC stärker dazu neigten, Ovarialmetastasen sowie Metastasen des Magen-Darm-Trakts zu entwickeln. Diese Information erlaubt den Klinikärzten, beim Screening gezielter nach Metastasen zu suchen; es verstärkt auch das Argument, dass diese 2 Brustkrebsvarianten als separate Erkrankungseinheiten zu behandeln sind.

Key words

lobular carcinoma - breast cancer - late recurrence - survival - distant - metastasis

Schlüsselwörter

lobuläres Karzinom - Brustkrebs - Spätrezidiv - Überleben - Fernmetastasen - Metastasierung

• References

• 1 Li CI, Anderson BO, Daling JR. et al. Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA 2003; 289: 1421-1424
• 2 Guiu S, Wolfer A, Jacot W. et al. Invasive lobular breast cancer and its variants: How special are they for systemic therapy decisions?. Crit Rev Oncol Hematol 2014; 92: 235-257
• 3 Arpino G, Bardou VJ, Clark GM. et al. Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res 2004; 6: R149-R156
• 4 Ciriello G, Gatza ML, Beck AH. et al. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 2015; 163: 506-519
• 5 Pestalozzi BC, Zahrieh D, Mallon E. et al. Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. Journal Clin Oncol 2008; 26: 3006-3014
• 6 Sikora MJ, Jankowitz RC, Dabbs DJ. et al. Invasive lobular carcinoma of the breast: patient response to systemic endocrine therapy and hormone response in model systems. Steroids 2013; 78: 568-575
• 7 Winchester DJ, Chang HR, Graves TA. et al. A comparative analysis of lobular and ductal carcinoma of the breast: presentation, treatment, and outcomes. J Am Coll Surg 1998; 186: 416-422
• 8 Hilleren DJ, Andersson IT, Lindholm K. et al. Invasive lobular carcinoma: mammographic findings in a 10-year experience. Radiology 1991; 178: 149-154
• 9 Le Gal M, Ollivier L, Asselain B. et al. Mammographic features of 455 invasive lobular carcinomas. Radiology 1992; 185: 705-708
• 10 Sawyer E, Roylance R, Petridis C. et al. Genetic predisposition to in situ and invasive lobular carcinoma of the breast. PLoS Genet 2014; 10: e1004285
• 11 Barroso-Sousa R, Metzger-Filho O. Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications. Ther Adv Med Oncol 2016; 8: 261-266
• 12 Desmedt C, Zoppoli G, Gundem G. et al. Genomic characterization of primary invasive lobular breast cancer. J Clin Oncol 2016; 34: 1872-1881
• 13 Lau M, Klausen C, Leung P. E-cadherin inhibits tumor cell growth by suppressing PI3 K/Akt signaling via β-catenin-Egr1-mediated PTEN expression. Oncogene 2011; 30: 2753-2766
• 14 Rakha EA, El-Sayed ME, Powe DG. et al. Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes. Eur J Cancer 2008; 44: 73-83
• 15 García-Fernández A, Lain JM, Chabrera C. et al. Comparative long-term study of a large series of patients with invasive ductal carcinoma and invasive lobular carcinoma. Loco-regional recurrence, metastasis, and survival. Breast J 2015; 21: 533-537
• 16 Korhonen T, Kuukasjärvi T, Huhtala H. et al. The impact of lobular and ductal breast cancer histology on the metastatic behavior and long term survival of breast cancer patients. Breast 2013; 22: 1119-1124
• 17 Lamovec J, Bračkko M. Metastatic pattern of infiltrating lobular carcinoma of the breast: an autopsy study. J Surg Oncol 1991; 48: 28-33
• 18 Borst MJ, Ingold JA. Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast. Surgery 1993; 114: 637-641 discussion 641–642
• 19 Switzer N, Lim A, Du L. et al. Case series of 21 patients with extrahepatic metastatic lobular breast carcinoma to the gastrointestinal tract. Cancer Treatment Communications 2015; 3: 37-43
• 20 Inoue M, Nakagomi H, Nakada H. et al. Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer. Breast Cancer 2017;
• 21 Fournier A, Fabre A, Mesrine S. et al. Use of different postmenopausal hormone therapies and risk of histology-and hormone receptor–defined invasive breast cancer. J Clin Oncol 2008; 26: 1260-1268
• 22 Li CI, Daling JR, Haugen KL. et al. Use of menopausal hormone therapy and risk of ductal and lobular breast cancer among women 55–74 years of age. Breast Cancer Res Treat 2014; 145: 481-489
• 23 Kuwabara Y, Yamada T, Yamazaki K. et al. Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis. Cancer Sci 2008; 99: 1933-1939
• 24 Guilford P, Hopkins J, Harraway J. et al. E-cadherin germline mutations in familial gastric cancer. Nature 1998; 392: 402-405
• 25 Adachi Y, Ishiguro J, Kotani H. et al. Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma. BMC Cancer 2016; 16: 1