Aneuploidy identifies subsets of patients with poor clinical outcome in grade 1 and grade 2 breast cancer.
OBJECTIVE
Histological grade is a well-established prognostic/predictive factor in breast cancer. However, mainly within intermediate categories, patients may have unpredictable outcome. We hypothesised whether ploidy status can distinguish different prognostic groups among breast cancer patients with similar tumour grade.


METHODS
The study involved 684 patients with invasive breast carcinoma, and median follow-up of 134.5 months. Pathological staging was evaluated according to WHO classification. Tumour differentiation was assessed using the Nottingham grading system. Ploidy was determined prospectively by DNA flow cytometry. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method.


RESULTS
There were 179 (26.2%) deaths and 239 (33.3%) disease recurrences. For grading, tumours were classified as follows: 163 (23.8%) G1, 356 (52.1%) G2 and 165 (24.1%) G3, while 389 (56.9%) tumours presented aneuploidy. Ploidy and grading are strongly associated (P < 0.001). Patients with aneuploid G2 tumours showed worse DFS (P = 0.001) and OS (P < 0.001), as well as those with aneuploid G1 tumours in relation to OS (P = 0.013). When a subset analysis was performed in early breast cancer patients (n = 451) with Stage I/IIA of disease, it remained the same significant associations of aneuploid G1 (to OS) and G2 tumours (to DFS and OS) with unfavourable prognosis.


CONCLUSIONS
Aneuploidy identifies subsets of breast cancer patients with G1 and G2 tumours who showed poor clinical outcome. The finding has therapeutic implications, as these patients are potential candidates to risk-adapted adjuvant therapy.
Serviço de Anatomia Patológica do Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), E.P.E., R. Prof. Lima Basto, 1099-023 Lisboa, Portugal. Electronic address: aepinto@ipolisboa.min-saude.pt.
António E
AE
Pinto
Serviço de Anatomia Patológica do Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), E.P.E., R. Prof. Lima Basto, 1099-023 Lisboa, Portugal. Electronic address: tpereira@ipolisboa.min-saude.pt.
Teresa
T
Pereira
Centro de Estatística e Aplicações e Departamento de Matemática do Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal. Electronic address: giovani.silva@tecnico.ulisboa.pt.
Giovani L
GL
Silva
Serviço de Anatomia Patológica do Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), E.P.E., R. Prof. Lima Basto, 1099-023 Lisboa, Portugal. Electronic address: sandre@ipolisboa.min-saude.pt.
Saudade
S
André
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005819:Genetic Markers; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers
Breast cancer; DNA ploidy; Flow cytometry; Prognosis; Tumour histological grade