Free Online Tool Predicts Late ER+ Breast Cancer Recurrence

Liam Davenport

June 05, 2019

CHICAGO — A readily available online tool, which relies on standard parameters gathered routinely in clinical practice, may be able to predict those women with oestrogen receptor-positive (ER+) breast cancer who have a low risk of a late distant recurrence, and who could therefore avoid continued endocrine therapy after 5 years, say UK researchers.

The data were presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting by Dr Juliet Richman, a specialist registrar in medical oncology, at The Royal Marsden NHS Foundation Trust, London.

Calculator Trialled

The Clinical Treatment Score at 5 years (CTS5) was developed by colleagues at the Royal Marsden Hospital using the Arimidex, Tamoxifen, Alone or in Combination (ATAC) dataset and validated with results from the BIG 1-98 trial of letrozole and tamoxifen in postmenopausal women with breast cancer.

The tool relies on just four variables collected routinely in clinical practice: tumour size; grade; lymph node burden; and patient age. It was previously shown to be highly prognostic for late disease recurrence.

To validate it in an unselected group of women, the researchers used the CTS5 Calculator, a freely available online tool for clinicians to predict late distant metastasis for women with ER+ breast cancer.

They examined the records of almost 2500 women, including more than 750 premenopausal women, finding that the CTS5 categorised approximately 41% as having a low risk of late distant recurrence of 5%.

In postmenopausal women, the score was significantly able to stratify them into low, intermediate, and high risk of late distant recurrence, but was only able to significantly distinguish low and high risk in premenopausal women.

Benefits Outweigh Risks

Invited to discuss the study, Dr Norah Lynn Henry, associate professor, Division of Oncology, University of Utah, Salt Lake City, in the US, said that the benefits of the first 5 years of therapy have been shown to outweigh the risks "for the majority of patients" with ER+ breast cancer.

"However, the relative benefits of this are less clear for years 6 to 10."

The question then becomes one of "which patients are more likely to benefit," especially given that almost half of recurrences occur after 5 years.

In such patients, additional interventions may be beneficial, but for those at low risk, they may confer only risks.

She said that the current results "clearly validated" the CTS5 as prognostic in postmenopausal women, although the calibration is "less impressive" for women who are premenopausal at the time of diagnosis.

It also requires testing in HER2+ disease, and it is noteworthy that "a substantial minority of patients received adjuvant therapy beyond 6 years, and it isn’t clear how this was accounted for in the analysis".

Dr Henry nevertheless said that the CTS5 tool may be "most useful for identifying patients at very low risk of disease recurrence", in addition to which it may be helpful in stratifying patients in clinical trials.

Study Details

To examine whether the CTS5 could be used in unselected women, Dr Richman and colleagues identified all women diagnosed with ER+ breast cancer treated at their institution between 2000 and 2007 who were alive and free of distant recurrence at 5 years.

They included 1662 postmenopausal women with an average age of 62.5 years, of whom 83.2% were HER2 negative.

The team reports that 28.2% were treated with chemotherapy, 79.3% received endocrine therapy for 48–72 months and 13.2% were treated for more than 72 months.

After a median follow-up of 9.3 years, distant recurrence was seen after five years in 9.0% of women, at a median time to distant recurrence of 8.3 years. In addition, 23.4% of women died after 5 years.

In addition, 766 premenopausal women were included, who had an average age of 46 years and 79.9% of whom were HER2 negative.

Chemotherapy was administered to 70.5%, while 62.8% were treated with endocrine therapy for 48–72 months and 23.8% received the drugs for more than 72 months.

A distant recurrence occurred after 5 years in 12.3% of women, after a median of 10.7 years, while 8.9% died after 5 years.

Increases in CTS5 scores were associated with a significant increase in the risk of late distant recurrence, at a hazard ratio of 1.95 in postmenopausal women (p<0.0001) and 1.72 in premenopausal women (p=0.001).

Compared with CTS5 low scores, postmenopausal with intermediate and high scores had a significantly increased risk of late distant recurrence, at hazard ratios if 2.28 (p=0.003) and 3.81 (p<0.0001), respectively.

In premenopausal women, the risk of late distant recurrence was significantly increased with CTS5 high scores compared to low scores, at a hazard ratio of 2.63 (p=0.008).

The association between CTS5 scores and distant late recurrence risk remained significant regardless of whether or not the women had received chemotherapy, apart from in premenopausal women who did not receive the treatment.

The results also showed that the CTS5 was able to stratify the postmenopausal women into risk groups in a similar way to that seen in the previous study, with 41.2% low risk, 33.0% intermediate risk, and 21.9% high risk.

The proportion of these women with late distant recurrence was 4.9%, 10.9%, and 16.9%, respectively.

Crucially, there was a close correlation between the observed versus expected events in postmenopausal women.

In premenopausal women, the separation was less distinct, with 41.0% low risk, 34.1% intermediate risk, and 24.9% high risk, and a proportion with late distant recurrence was 4.9%, 8.5%, and 12.0%, respectively.

Stopping Treatment

Dr Richman told Medscape News UK that not all women in the UK with ER+ breast cancer continue with endocrine therapy after 5 years, and it can depend on how they feel about treatment.

She explained that some women think of the tablet as a "daily reminder" of the "horrendousness" of what they went through, "and they just don’t want to continue".

Others are "absolutely risk averse" and would continue with treatment for the rest of their life if they were told to do so.

Dr Richman noted that alongside the psychological burden of ongoing treatment, there is also a physical burden, as "these drugs are not without their toxicities", and there is a financial burden.

While the current findings suggest it is possible to use the CTS5 score to identify women who can stop endocrine therapy after 5 years, the researchers would like to test it in an extended endocrine therapy trial to see if that played out in practice.

Also, they acknowledge that, with the study having included only women referred to a tertiary referral centre, their demographic characteristics may not reflect other areas of the UK.

Dr Richman said: "One of the limitations of the study is that it is single centre, and not only is it single centre but it is in a really specialist place where women are self-selecting, they seek us out."

She continued: "While we do have people coming from afar and we do have different socioeconomic and racial backgrounds, we probably don’t have as good a spread as we would have if we’d picked two or three other centres and done the study there.

"I think that would be useful work for someone to take on from there."

Nevertheless, Dr Richman underlined that the advantage of CTS5 is that it uses variables "that are measured routinely in every woman when she’s treated for breast cancer, so this is nothing that requires a special, additional test".

No funding declared.

Richman declares no conflicts of interest. Other authors disclose several potential conflicts.

Henry reports Research Funding - Abbvie (Inst); H3 Biomedicine (Inst); Innocrin Pharma (Inst); Pfizer (Inst).

American Society of Clinical Oncology (ASCO) 2019 Annual Meeting. Presented June 2, 2019. Abstract 514.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.