Early Breast Cancer Detection ‘Remains Vital’

Tumour size and nodal spread are still the main influences on breast cancer survival

  • Date: 08 Oct 2015
  • Author: Lynda Williams, Senior medwireNews Reporter
  • Topic: Breast Cancer

medwireNews: Tumour stage at the time of detection remains a significant predictor of breast cancer patient survival even with recent developments in systemic therapy and increasing use of breast-conserving surgery, Dutch researchers have found.

Overall mortality significantly correlated with increasing tumour stage and lymph node positivity in 80,228 women diagnosed with primary breast cancer between 1999 and 2005 and 93,569 patients whose disease was detected between 2006 and 2012, the team reports in The BMJ.

Madeleine Tilanus-Linthorst, from Erasmus University Medical Centre in Rotterdam, and co-authors, who collated data from the Nationwide Netherlands Cancer Registry, therefore emphasize: “Diagnosis of breast cancer at an early tumour stage remains vital.”

After adjusting for patient age, tumour grade, stage and morphology, treatment and the presence or absence of a second primary breast cancer, the risk of overall mortality in the earlier patient population significantly rose with increasing pathological tumour stage and node category.

Compared with women with T1a disease diagnosed between 1999 and 2005, the hazard ratio (HR) for mortality rose from a significant 1.40 in those with T1c disease to 2.77 for patients with T4 stage. And compared with N0 patients, those with N2 and N3 status had HRs for mortality of 2.19 and 3.48, respectively.

The risk of overall mortality remained significantly associated with tumour size over 1 cm and nodal stage among women diagnosed between 2006 and 2012, after taking into consideration a raft of confounding factors including tumour hormone receptor status and HER2 status.

Compared with women with T1a tumours, the HR for overall mortality among those with T1c, T2, T3 and T4 disease were a significant 1.54, 2.17, 2.78 and 3.32, respectively. And using N0 status as the comparator, patients with N1, N2 and N3 disease had significant HRs for mortality of 1.25, 2.36 and 4.0, respectively.

Other significant risk factors for overall mortality in this later population included increasing tumour grade (grade 2 and 3 vs 1, HR=1.18 and 1.69, respectively), positive oestrogen status (HR=0.71 vs negative), and positive or unknown progesterone receptor status (both HR=0.81 vs negative), and unknown or inconclusive HER2 status (HR=0.94 vs negative).

“Apparently, trastuzumab is so effective that, with its current use in tumours larger than 1 cm, the effect of HER2 positivity on survival becomes negligible”, comment the authors.

“The group with unknown HER2 status contained a large number of patients with inconclusive HER2 status, who might well be HER2 positive but who did not all receive targeted therapy. This group had significantly higher hazard rates, which endorses the necessity of targeted therapy in HER2 positive patients.”

Breast conserving surgery had a significant HR for overall mortality of 0.87 compared with mastectomy, whereas choosing no surgery had a significant HR of 4.1. Receipt of axillary lymph node dissection was associated with a significant HR of 1.29 versus no dissection.

Discussing the findings in an accompanying editorial, Ines Vaz-Luis and Harold Burstein, from Harvard Medical School in Boston, Massachusetts, USA, comment: “Of late, there has been debate about whether mammography saves lives or whether, in a modern era of effective therapy, detecting cancers when they are smaller makes any meaningful difference to patients.

“Saadatmand and colleagues’ study does not specifically answer the question. But it strongly suggests that, even after accounting for biological variation in tumours and enhanced treatments, tumour stage at diagnosis still matters”, they write.

“That is a powerful albeit indirect argument in favour of screening mammography. Catching cancers when they are smaller still makes a difference.”


Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MMA. Influence of tumour stage at breast cancer detection on survival in modern times; population based study in 173 797 patients. BMJ 2015; 351: h4901 6 October. dx.doi.org/10.1136/bmj.h4901

Vaz-Luis I, Burstein HJ. With better adjuvant therapy, does breast cancer stage still matter? BMJ 2015; 351: h5273 6 October. dx.doi.org/10.1136/bmj.h5273

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