nina, I don't really have answers to your questions, but did have a 21 onco score. My MO left it up to me as whether or not I wanted to do chemo. My tumor was larger than yours and a higher grade. It was also close to my chest wall. I have a family history, although there is no BRCA gene associated. So, I was aggressive in my treatment. I believe chemo is said to be more effective on the higher vs lower grade tumors...best of luck with your treatment plan!

Re: "There is a major study ongoing (Tailorx) looking at outcomes for intermediate oncotype scores with or without chemo (but that study excludes subjects with tumors less than 1 cm)."

That does not appear to be accurate. The TAILORx trial did include certain patients with tumors less than 1 centimeter, although these are less common than larger tumors. According to the recent TAILORx publication reporting interim 5-year results for those with Recurrence Scores of 0 to 10 (assigned to receive endocrine therapy alone), the following patients were included in the trial:

Sparano (2015), "Prospective Validation of a 21-Gene Expression Assay in Breast Cancer"

Main page: http://www.nejm.org/doi/full/10.1056/NEJMoa1510764#t=article

PDF version: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1510764

"Study Patients

The study included women 18 to 75 years of age with axillary node–negative invasive breast cancer that was estrogen-receptor–positive or progesterone-receptor–positive (or both) and that did not overexpress HER2. Patients had to meet National Comprehensive Cancer Network guidelines for the recommendation of adjuvant chemotherapy,[21] including a primary tumor size of 1.1 to 5.0 cm in the greatest dimension for a tumor of any grade or a size of 0.6 to 1.0 cm in the greatest dimension for a tumor of intermediate or high histologic grade or nuclear grade (or both)."

In addition, Table 1 of Sparano indicated that 128 of 1626 (or 8%) of the patients with Recurrence Scores of 0 to 10 had tumors "<1.0 cm" in greatest dimension, and that 568 of 6883 (or 8%) of the patients with Recurrence Scores of 11–25 had tumors "<1.0 cm" in greatest dimension.

Unfortunately, the trial is on-going and we are still awaiting the results for the group of patients with scores of 11 to 25.

BarredOwl

My oncotype was 26, and my MO said that I needed chemotherapy. I had a 1.2 cm tumor in my left breast, grade 2. The surgical pathology report also revealed DCIS in the left breast, which was also grade 2. I had a bilateral masectomy in February. According to the oncotype, my risk of distant recurrence within the next 10 year she was 17 percent with only 5 years of tamoxifen.

Meow, all of the validating studies were done w/tamoxifen.

While waiting for TailorX results, MD Anderson Cancer Center in Texas decided to retrospectively look at their own intermediate OncoDX patients (with and without chemo) and found this:

More patients with early-stage breast cancer may be able to avoid chemotherapy in the future

https://www.mdanderson.org/newsroom/2017/02/more-p...

Hi Nina -

my oncotype was 25 as well and I had 4 tumors all under 2cm with the largest 1.9cm. My MO was on the fence but ultimately decided against Chemo. I got a second opinion from Dana Faber in Boston and they also confirmed that Chemo would only better my chances of non-recurrence by only 2 or 3%. So we all decided against Chemo. I had however a mastectomy and radiation and am now on Tamoxifen.

All the best to you

Hi ninaoctober, thanks for posting this.

I am in a similar situation: Stage 1A; post menopause; 8mm tumor; ER +; oncotype 19. I too saw that the medical community is waiting for this TailorX study, which my oncologist confirmed. She was very clear that she had no statistical evidence that the chemo would help because the benefits were at most a 4% reduction in risk, which was within the margin of error.

I have four weeks to make my decision. I'm seeking second and third opinions. But, I don't have any wisdom or new information yet.

I so appreciate everyone's input.

Sending everyone love and appreciation.

getting the Mammaprint test seems logical. Likewise, have your case presented to the hospital's tumor board...

And, yes! What is most fascinating about these genetic tests is that they are now trumping tumor characterestics with respect to clinical treatment decisions. Since being included in the NCCN's 2011 bresst cancer treatment guidelines, the more subsequent research has certainly proven interesting. It is quite interesting to note that there are a small percentage of tumors with favorable characterestics but have high OncotypeDX scores, while some with less favorable characteristics have low scores. That fact underscores the need for genetic tests that can help guide treatment decisions. Likewise, the Anderson study is interesting too. For many patients, breast cancer is becoming a highly treatable disease with better individualized treatment.

The MD Anderson press release includes some important comments from the lead author:

"The study has a number of limitations, said Barcenas. Due to a relatively short follow-up and the few number of outcome events, the researchers feel that the benefit of chemotherapy cannot be ruled out yet in this group of patients.

While not practice changing, the findings do give Barcenas more information when discussing the benefits of chemotherapy in early-stage breast cancer patients, should their RS score be 11-25."

Unfortunately, the full-length research article is behind a paywall:

Barcenas (2017): http://onlinelibrary.wiley.com/doi/10.1002/cncr.30618/full

1424 patients were studied, using the investigational risk ranges from the TAILORx trial:

RS = 0 to 10 (297 patients; 21%): 1.7% of these received chemotherapy;

RS = 11 to 25 (894 patients; 63%): 15% of these received chemotherapy;

RS > 25 (233 patients;16%): 73.4% of patients of these received chemotherapy.

Note: Standard risk ranges for the OncotypeDX test for invasive disease are 0 to 17 ("Low Risk"); 18 to 30 ("Intermediate Risk"); and 31 to 100 ("High Risk").

The MD Anderson study was a retrospective study based on clinical usage, so it appears that decision-making about chemotherapy was at the discretion of patients and their physicians.

The second group with Recurrence Scores of 11 to 25 included both patients with Recurrence Scores of 11 to 17 (i.e., in the standard "Low Risk" range) and patients with Recurrence Scores of 18 to 25 (i.e., in the standard "Intermediate Risk" range). My layperson impression is that the inclusion of those with scores of 11 to 17 could conceivably contribute to certain favorable findings, as well as potentially limit the potential benefit of added chemotherapy, seen in the 11 to 25 group as a whole (or say, perhaps, in a subgroup scoring 18 to 25).

I note that the TAILORx trial protocol suggests that the planned analysis includes certain outcomes by small increments in Recurrence Score within the 11 to 25 group (who were randomized to receive endocrine therapy alone OR endocrine therapy plus chemotherapy) to probe whether a subset within the 11 to 25 cohort may benefit from added chemotherapy. The results from this trial cannot come fast enough.

It is not really possible to evaluate the implications of a full-length paper from a press release or abstract. Those with pending treatment decisions interested in these findings should be certain to discuss them with their Medical Oncologist, to ensure proper weight is given to its findings.

BarredOwl

If you want a clearer picture about your risk, I would suggest asking about MammaPrint+BluePrint (which also classifies whether your tumor is Luminal A vs. or Prosigna. Both of these tests have no “intermediate risk" category—just “high" or “low." One woman on this board with an ODX of 20 came back “high risk" on Prosigna and got chemo; the other, with an ODX of 23, came back “low risk, Luminal A" on MammaPrint+BluePrint and skipped chemo.

In your case, I think you should read between the lines of what your MO is saying in recommending against chemo and perhaps even endocrine therapy: your age. At 68, you would likely have a much tougher time than you did at 48 with chemo (including comorbidities that may have arisen in those intervening years). As to the endocrine therapy, we who are way past menopause tend to either experience fewer SEs from AIs or don't notice them as much because of all the aging we've already done. And an AI, if taken now, would probably be more effective than the Tamoxifen you took 20 years ago (when AIs were used mainly as third-generation fertility drugs or by male bodybuilders to suppress the estrogens that could cause gynecomastia in steroid users and interfere with extreme muscle development). Perhaps your MO is supposing that you might not want to afflict your golden years with AI side effects…but you might not get them anyway.

Another thing an OncotypeDX test does not take into account is how aggressive a particular tumor would be in a younger vs. an older woman. It does not test the patient at all—only a ground-up piece of her tumor, regardless of where and in whom it grew. In a woman of 68, a tumor with an ODX score of 25 would likely be more “indolent" (slow-growing) than would a tumor scoring 18 in a premenopausal woman. Consider your quality of life, as well as your life expectancy regardless of cancer. If you are destined to make it into your 80s (as we both statistically are), how would you like to live those years? Which would you consider less endurable—side effects (which might be mild) or worry (which might be unfounded)? I stopped worrying—it is what it is. I've already lived longer than three out of four of my grandparents and half my aunts & uncles. (Not to mention eight of my friends). I still have a very long bucket list, and I'd prefer to be in a condition to enjoy as much of its items as I can to the fullest even if I never get to complete it. (I can't see myself skydiving or cruising to Antarctica at 90).

In my post above, I noted:

"In some cases (but not always), a second multiparmeter test might be ordered (e.g., MammaPrint plus BluePrint, Prosigna), if under applicable criteria (including "Clinical Risk" for MammaPrint) such further testing may provide additional information of value to decision-making. However, such secondary testing is not always recommended and appears to be less common outside of the United States."

Patients who do receive such secondary testing may or may not receive a clear signal.

MammaPrint: Is it black and white?

Please confirm the following with a professional. MammaPrint may have a "binary" output (High Risk or Low Risk), but as a result of the design of the MINDACT trial and the available 5-year results pertaining to "discordant" groups, the test appears appears to yield less clear information in many patients.

Results from the MINDACT trial with 5 years of follow-up were recently published (Cardoso (2016)). This is a highly detailed and technical publication, so I refer others to the original. The documents can be accessed here:

Cardoso (2016):

Main Page: http://www.nejm.org/doi/full/10.1056/NEJMoa1602253

PDF version (Free): http://www.nejm.org/doi/pdf/10.1056/NEJMoa1602253

Supplementary Appendix (Free): http://www.nejm.org/doi/suppl/10.1056/NEJMoa1602253/suppl_file/nejmoa1602253_appendix.pdf

Hunter perspective (2016) (Free): http://www.nejm.org/doi/pdf/10.1056/NEJMp1608282

Hudis editorial (2016): http://www.nejm.org/doi/pdf/10.1056/NEJMe1607947

(Available for purchase)

The MINDACT trial design incorporated two risk classifications. It used a Clinical Risk Classification (using a MODIFIED version of Adjuvant! Online) to assign clinical risk as either "Clinical Low Risk" or "Clinical High Risk". It used a Genomic Risk Classification (using the MammaPrint test result) to assign genomic risk as "Genomic Low Risk" or "Genomic High Risk".

This yielded four different study groups (MP = MammaPrint):

(a) Clinical Low / Genomic MP Low

(b) Clinical High / Genomic MP Low ("discordant")

(c) Clinical Low / Genomic MP High ("discordant")

(d) Clinical High / Genomic MP High

The group that is Low Risk by both criteria (Group (a)) and the group that is High Risk by both criteria (Group (d)) are "concordant" (same: Low Low or High High).

The two groups that have different clinical and genomic risks (one Low and one High) are "discordant" (Groups (b) and (c)).

Part of the study looked at whether directing chemotherapy decisions on the basis of genomic risk or on the basis of clinical risk led to any difference in distant recurrences in the "discordant" groups. In certain groups, the test was not found to give a very clear signal regarding the potential benefit of added chemotherapy, (although due to differences in risk tolerance, patients may have differing views on this). The study had some limitations. For example, the study was not adequately powered to demonstrate the statistical significance of some differences between groups for all endpoints. (A medical oncologist should be able to explain possible caveats arising from these limitations.) In any event, the clarity of the information provided by the test and the medical advice received in light of same, will likely differ according to these groupings.

Prosigna: Some cases appear to yield an "Intermediate" result

Please confirm it with a professional, but it appears the Prosigna test may in some situations provide an "Intermediate" risk output. The following screen shot is taken from the Package Insert, which seems to suggest that test outputs differ by Risk Category, and that the test yields "Low, Intermediate, High" outputs in the node-negative setting.

http://prosigna.com/wp-content/uploads/2016/09/LBL_C02223_06_Package-Insert-Prosigna-Assay-US.pdf

Of course, patients should never hesitate to inquire with their medical oncologist about such additional testing.

BarredOwl

This is a useful article regarding the test, early study publications, and the rationale for the TAILORx trial design:

Sparano and Paik (2008): "Development of the 21-Gene Assay and Its Application in Clinical Practice and Clinical Trials"

http://ascopubs.org/doi/pdf/10.1200/JCO.2007.15.1068

For those with node-negative (N0) disease and a Recurrence Score of 0 to 10, the TAILORx trial publication cited earlier in the thread reporting interim 5-year results for those with Recurrence Scores of 0 to 10 (assigned to receive endocrine therapy alone) is noteworthy:

Sparano (2015), "Prospective Validation of a 21-Gene Expression Assay in Breast Cancer"

Main page: http://www.nejm.org/doi/full/10.1056/NEJMoa1510764#t=article

PDF version: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1510764

In other threads, some members inquired about the use of an Aromatase Inhibitor instead of Tamoxifen. Although the Oncotype reports currently feature "validation" studies in which Tamoxifen was used, this reflects historical and practical considerations of clinical trial design. In current practice, the use of OncotypeDX Recurrence Score information does not restrict choice of endocrine therapy.

For example, a later Oncotype "validation" study was conducted in patients who had received 5-years of the aromatase inhibitor Anastrozole. This study used samples and 9-yr recurrence rates from the tamoxifen arm and the anastrozole arm of the ATAC trial, in node-negative and node-positive postmenopausal women with localized breast cancer.

Dowsett (2010), "Prediction of Risk of Distant Recurrence Using the 21-Gene Recurrence Score in Node-Negative and Node-Positive Postmenopausal Patients With Breast Cancer Treated With Anastrozole or Tamoxifen: A TransATAC Study"

http://jco.ascopubs.org/content/28/11/1829.full.pdf

I note that the TAILORx protocol permitted choice of endocrine therapy. For example, Sparano (2015) notes:

"In the low-risk cohort of 1626 patients [scoring 0 to 10], endocrine therapy included an aromatase inhibitor in 963 patients (59%), tamoxifen in 560 (34%), sequential tamoxifen followed by aromatase-inhibitor therapy in 13 (1%), ovarian-function suppression in 44 (3%), or other or unknown therapy in 46 (3%)."

There are hundreds of articles and abstracts available regarding the test in the node-negative and node-positive settings. If a publication influences your thinking in any way, it is essential to confirm your understanding, as well as currency and applicability to your case, with your Medical Oncologist.

BarredOwl

Hi ninaoctober:

I think there is a restriction on including links until after a certain number of posts (to discourage spam), and you may only have just reached the threshold.

You may already know this, but once you qualify to insert a link, then to ensure your links are operational, it is best to use the "Link" tool located above the text entry field where various formatting and insert options can be found (Bold, Italic, Strikeout, List bullets, etc).

The fourth option from the far right is the Link tool (line inside of rounded brackets).

Copy the link; Click on the Link tool (-); Select Insert Link; Paste link into the URL field, and click insert.

BarredOwl

I have read many similar articles indicating people with an intermediate oncotype dx score can safely skip chemo. My frustration is the intermediate scores in the relevant TAILORX study ranges from 19 to 25. Would appreciate your thinking on how would the outcome of this study help people with higher intermediate score 26 to 30? Thank you

Rameson