Need Studies on Breast Cancer prognosis beyond 10 years

Why did they tell you you have a high likelihood of dormant cancer stem cells still floating around? Your stats seem favorable and your treatment very aggresdive

Hi mytwocents:

Re: "The test said I had a 25% recurrence rate with a long-term recurrence rate of 15%. Since I was in the intermediate risk category. . . "

While the content of the reports from 2006 may differ from those of 2016, the node-negative (N0) validation studies, and the relationship between Recurrence score and average recurrence risks based on those studies, would be the same. The standard risk categories have not been changed:

Paik (2004): http://www.nejm.org/doi/pdf/10.1056/NEJMoa041588

Paik (2006): http://jco.ascopubs.org/content/24/23/3726.full.pdf

In these validation studies, all patients received tamoxifen. Currently, all recurrence risk information in the node-negative report is based on patients who received (a) endocrine therapy alone; or (b) endocrine therapy plus chemotherapy.

I am wondering if the "10-year risk of distant recurrence after 5-yrs of tamoxifen" based on your Intermediate Recurrence Score was actually 15%. Please check the content of your original report.

Based on the current sample node-negative report available on-line and the validation study of Paik (2004) above (Figure 4), in the intermediate range, the average 10-year risk of distant recurrence after 5-yrs of tamoxifen tops out around 20% (see graph below). An inspection of the graph shows that an average 10-yr risk of 25% would be somewhere in the high risk group.

Sample node-negative (N0) Oncotype report:

http://breast-cancer.oncotypedx.com/en-US/Professional-Invasive/Ordering/ReadingTheReports/Node-NegativeReport

Top graph from sample report:

Current Oncotype reports do not provide risk information without endocrine therapy. This is because the patients in the validation studies featured in the reports all received endocrine therapy at least.

Is it possible that the 25% risk estimate was your MO's independent estimate of recurrence risk without endocrine therapy (e.g., extrapolated from the average 15% 10-yr risk with endocrine therapy based on the risk reduction benefit of tamoxifen)? Please ask your MO.

BarredOwl

Hi mytwocents:

Regarding your specific question, such studies are not that common due to the challenges of long-term follow-up. There are also some inherent limitations with extended follow-up periods.

Colleoni et al. recently reported results of one study in both ER+ and ER- patients with a median follow-up of 24-years from diagnosis of operable breast cancer. Results from five prospective and randomized IBCSG studies, including 4,105 patients randomly assigned from 1978 through 1985 were reported. With such long-term follow-up, there have been changes in systemic treatments and radiation therapy, so that patients diagnosed more recently may fare better. In addition, the study population was relatively diverse, so those with more favorable prognostic features may also tend to fare better than than the group as a whole. I suspect both of these would apply to your situation.

They found that ER+ patients (like everyone else) were at greatest risk in the first 5 years, and that the hazard decreases thereafter. There is a table in the original paper with hazard of recurrence by 5-year intervals according to ER status (ER+ versus ER-) among various subgroups defined by number of positive axillary nodes, tumor size, grade, menopausal status or treatments (observation, chemotherapy alone, hormonal therapy +/- chemotherapy).

Colleoni (2016): http://jco.ascopubs.org/content/34/9/927.abstract

(A complete pdf copy of the paper can be obtained for a small fee (currently $2.00) via the PatientACCESS option, with free registration at the Copyright Clearance Center.)

"Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V"

Marco Colleoni, Zhuoxin Sun, Karen N. Price, Per Karlsson, John F. Forbes, Beat Thürlimann, Lorenzo Gianni, Monica Castiglione, Richard D. Gelber, Alan S. Coates and Aron Goldhirsch

"Abstract

Purpose Predicting the pattern of recurrence can aid in the development of targeted surveillance and treatment strategies. We identified patient populations that remain at risk for an event at a median follow-up of 24 years from the diagnosis of operable breast cancer.

Patients and Methods International Breast Cancer Study Group clinical trials I to V randomly assigned 4,105 patients between 1978 and 1985. Annualized hazards were estimated for breast cancer–free interval (primary end point), disease-free survival, and overall survival.

Results For the entire group, the annualized hazard of recurrence was highest during the first 5 years (10.4%), with a peak between years 1 and 2 (15.2%). During the first 5 years, patients with estrogen receptor (ER) – positive disease had a lower annualized hazard compared with those with ER-negative disease (9.9% v 11.5%; P = .01). However, beyond 5 years, patients with ER-positive disease had higher hazards (5 to 10 years: 5.4% v 3.3%; 10 to 15 years: 2.9% v 1.3%; 15 to 20 years: 2.8% v 1.2%; and 20 to 25 years: 1.3% v 1.4%; P < .001). Among patients with ER-positive disease, annualized hazards of recurrence remained elevated and fairly stable beyond 10 years, even for those with no axillary involvement (2.0%, 2.1%, and 1.1% for years 10 to 15, 15 to 20, and 20 to 25, respectively) and for those with one to three positive nodes (3.0%, 3.5%, and 1.5%, respectively).

Conclusion Patients with ER-positive breast cancer maintain a significant recurrence rate during extended follow up. Strategies for follow up and treatments to prevent recurrences may be most efficiently applied and studied in patients with ER-positive disease followed for a long period of time."

And from the full-text:

"For the entire group, the annualized hazard of breast cancer recurrence was greatest for the first 5 years (10.4%), with a peak interval between years 1 and 2 after surgery (15.2%; Fig 2A). The hazard decreased consistently during years 5 to 10 (4.5%) and then remained stable. During years 10 to 15, 15 to 20, and 20 to 25, the hazard of recurrence was 2.2%, 1.5%, and 0.7%, respectively (Table 2)."

Please note the following:

-- For the entire group, the annualized hazard of recurrence was highest during the first 5 years.

-- For the entire group, the annualized hazard of recurrence showed a peak between years 1 and 2 after surgery.

--The hazard fell off in years 5 to 10, and then persisted at a low level over time, particularly for ER+ disease.

-- Comparing ER+ versus ER-, they observed a statistically significantly lower hazard of breast cancer recurrence for patients with ER+ disease versus those with ER- disease during the first 5 years (9.9% v 11.5%; P = .01). However, the hazards of ER+ and ER- disease crossed between years 2 and 3, and beyond 5 years, the hazard of recurrence was higher for patients with ER+ disease compared with that of those with ER- disease.

NOTE: This is NOT saying that that the annualized hazard of ER+ patients increases after 5-years, but only that their annualized hazard remained higher than that faced by ER- in later time periods.

Unfortunately (and fortunately), long-term follow-up studies are hampered by being tied to the treatments and understanding of their time. To get ~24-year follow-up, patients were randomized in years 1978 through 1985. Yet concepts such as "intrinsic molecular subtype" (e.g., luminal, basal, etc) were first described by Perou more recently in 2000.

Again, regarding the specific hazard rates, with such long-term follow-up, there have since been improvements in systemic treatments and radiation therapy. Perhaps this study is more interesting for the trends observed, rather than the absolute hazard rates. Studies that reflect individual diagnosis and treatments as closely as possible may be better guides for patients, but unfortunately, they often do not have such long-term follow-up.

BarredOwl

Hi wallycat:

I have heard the same thing said of ER+ positive cancers as a group, but that assertion appears to be refuted by the findings of Colleoni et al. (2016).

Unfortunately, Colleoni (2016) does not appear to refer to "lobular" or "ILC". However, they do note: "In particular, the ER-positive subgroup is highly heterogeneous and might be separated into different subpopulations (eg, luminal A or that could behave differently during extended follow-up."

If you would like to look into the question about ILC further, here is a 2014 review article with citations to a variety of studies that looked at the ILC subset (not entirely consistent with each other). See Part II, page 243.

Guiu (2014) Review: http://www.croh-online.com/article/S1040-8428(14)00129-2/pdf

BarredOwl

I just want to point out that we don't have this information, nor should we expect to. I realized very early on that data going out 10 years measures the effectiveness of treatment TEN YEARS AGO, not current standard of care. So anything 20 years ago would measure treatment prior to anti-hormonals being standard of care, not to mention anything else that we take as routine today.

I am being followed for 15 years as part of the clinical trial I participated in, so we will have most of this information about 10 years from now.

I can say that as we layer in more treatment options, long term survival is improving greatly. And I also believe that once we get to truly personalized medicine as standard, it will increase exponentially. But that is a few years out. We do the best we can with the options available.

And then follow what is recommended to the extent possible. That is really the best we can do. After all, life comes with no guarantees. - Claire