Grade 1 ILC - response to neoadjuvant chemotherapy?

I had the oncotype test and scored low, so I skipped chemo. I had one positive node, had mastectomy and radiation. Insurance covered the test. Not sure what the current standards are, others here on the boards know more than I, but many women with 1-3 positive nodes get the test - not sure about insurance coverage. I hope someone will chime in here about chemo working for their ILC - there are many here who have had chemo. Good luck with your planning.

Hi there, Chemist.

You wrote that you have 3-4 positive nodes per MRI and 7 per ultrasound.

I'm surprised to read that your MRI can tell how many positive nodes you have. Ditto for the ultrasound. I had a needle biopsy to confirm that I had a positive node, but they weren't able to tell how many, either prior to chemo or after. That had to wait until surgery. They don't even know how many axillary lymph nodes we have until they are removed.

How have your docs determined that the hormone therapy isn't working (unfortunately)? May I ask what scans have you had, and how long you've been on the anti-hormonal?

Hi, I had ILC stage 1 in 2006. It was treated with lumpectomy, radiation and tamoxifen. All was well until 2010 and I had a recurrence in and on the same breast. This time we did chemo first to watch the skin lesions disappear and they did, however after a double mastectomy, they found traces of ILC still in bad breast. Thus, the chemo did some good but didn't get it all. I have been on Arimidex since then and no trouble with ILC coming back. I had the oncotypedx done in 2006 and my score was only a 9. Good luck with your treatments and remember this too shall pass and your new normal life will go on. If anxiety gets too much, ask for medication. It has helped me get thru the last 10 years:)

Hi Chemist:

Thank you for your reply. "SNLB" is sentinel lymph node biopsy.

(1) 5-years of Endocrine Therapy (e.g., tamoxifen, Aromatase Inhibitors)

The recurrence risk information provided in the Oncotype reports is sometimes said to "assume" 5-years of tamoxifen. This is because, in the validation studies featured in the Node Negative (N0) report and in the Node-Positive (N+) reports, all of the patients received either (a) 5 years of tamoxifen; or (b) chemotherapy plus five years of tamoxifen. Thus, patients should receive 5-years of endocrine therapy, or their recurrence risks would be much higher than shown in their report. However, this does not preclude the use of other approaches to endocrine therapy, including aromatase inhibitors.

A different validation study assessed the test 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 arms of the ATAC trial, in node-negative and node-positive postmenopausal women with localized breast cancer.

"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"

Dowsett (2010): http://jco.ascopubs.org/content/28/11/1829.full.pdf

The ongoing prospective TAILORx trial (in certain node-negative (N0) patients) is not limited to tamoxifen. The recent 2015 publication shows that a variety of approaches to endocrine therapy were used in the low risk cohort:

Sparano (2015): http://www.nejm.org/doi/full/10.1056/NEJMoa1510764#t=article

"In the low-risk cohort of 1626 patients, 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%). "

Similarly, per clinicaltrials.gov, the ongoing prospective RxPONDER trial (in certain node-positive patients) also includes various approaches to endocrine therapy:

https://clinicaltrials.gov/ct2/show/record/NCT01272037?term=Rxponder&rank=1

"Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity."

(2) Use of Biopsy Tissue

Excellent point. While surgical samples are more common in the adjuvant setting (for the reasons noted below), the test can also be performed on biopsy samples. Indeed, some members here have had the test done on a biopsy sample.

For others with a surgery first treatment plan, the Oncotype test is usually run on surgical samples, as explained here:

Timing: http://breast-cancer.oncotypedx.com/en-US/Patient-Invasive/WhatIsTheOncotypeDXCancerTest/WhenShouldTheOncotypeDXBreastCancerTestBeUsed.aspx

Surgical samples are more likely to be available in sufficient quantity and quality for conducting the test. With respect to quality, samples submitted must be suitably prepared and should be sufficiently "representative". For example, the submission form states: "List the most representative specimen (i.e. the highest grade and largest tumor) on line one." The selection of "representative" tissues is best made with full surgical pathology available.

Since nodal status is another element of "eligibility" or suitability for the test, axillary staging should typically be completed when eligibility is determined. This is another reason why eligibility is usually determined post-surgery.

(3-4) Nodal Status and Lymph Node Positive Reports

(a) Commercial availability of the test, (b) "Formal eligibility" requirements, (c) inclusion in clinical guidelines, and (d) insurance coverage are separate questions and may not all be in alignment, depending on the situation.

Insurers may not agree to pay with 4+ positive nodes, as noted by your MO. Regardless of lymph node status, an insurer may also balk at paying for the test in a person who received neoadjuvant treatment, because of concerns relating to the scope of validation in the neoadjuvant setting and/or ambiguity about nodal status (due to neoadjuvant treatment). Therefore, please work with your MO's office and Genomic Health to ensure you will not be hit with a ~ $4000 bill.

The formal eligibility is up to 3+ nodes. However, the commercial availability of the test includes 4+ nodes.

The submission form includes an area for specifying lymph node status:

The instructions note:

"*Node Status:

Enter the node status for the patient in the designated area. The node status is required to determine the extent of the clinical experience information to be included in the report for your patient. If the node status is not provided, a report with clinical experience for both node negative and node positive specimens will be sent. Additionally, the node status may be required for payor coverage determinations. If the node status is not specified, GHI may use the pathology report, if provided, to determine the node status for reimbursement purposes."

With one known positive node and some ambiguity regarding nodal status introduced by receipt of neoadjuvant endocrine therapy, you would probably want the clinical experience information for both Positive (1-3) and Positive (4+), but that is just my layperson guess.

While the formal eligibility is up to 3+ nodes, there is a sample Node Positive (≥ 4 N+) Report available on-line here:

http://breast-cancer.oncotypedx.com/en-US/Professional-Invasive/Ordering/ReadingTheReports/Node-PositiveOver4Report.aspx

The Node Positive (≥ 4 N+) Report appears to be based on the same validation study as the Node Positive (1-3 N+) Report (EDIT: Note the results for these groups are separately presented, and the 4+ group has higher recurrence rates):

Albain et al. (2010): http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70314-6/abstract

A pdf copy of Albain is available here (scroll down): Research Gate PDF

Note that the node-positive reports are quite different from the node-negative reports, because they are based on a different clinical validation study done in node-positive patients, and this study used a different kind of clinical endpoint. Hence, the graph in the node-positive reports provide information regarding 5-yr risk of recurrence or mortality after 5 yrs of tamoxifen as a function of Recurrence Score. (For more details, see the "Clinical Experience" section above the graph in the sample report, Figure 6B of Albain and related discussion.)

My understanding is that the node-positive validation study was in the adjuvant setting, so patients would have received surgery first. This is somewhat different from your situation, which you may wish to discuss with your MO.

Whether clinical consensus guidelines support the use of the Oncotype test in various situations is a separate question from its commercial availability or formal eligibility requirements. Guidelines consider the scope and quality of clinical validation, and make judgment calls about whether the prognostic and predictive capability of the test has been sufficiently established in various sub-groups, such that it in the appropriate case, it would be reasonable to withhold chemotherapy based on the Recurrence Score.

NCCN guidelines (Version 2.2016) treat the use of the test in node-positive patients quite differently than in node-negative patients. For node-positive patients (one or more metastases >2 mm to one or more ipsilateral axillary lymph nodes), the guidelines recommend Adjuvant endocrine therapy + adjuvant chemotherapy. The test is referred to in a footnote, noting that "[t]he 21-gene RT-PCR assay recurrence score [from the Oncotype test] can be considered in select patients with 1–3 involved ipsilateral axillary lymph nodes to guide the addition of combination chemotherapy to standard hormone therapy."

The recent ASCO guidelines take a particularly cautious approach with regard to node-positive disease. This is a technical document with a particular posture, and is a snap-shot in time in a rapidly developing field. It does not mandate any particular course of medical care, nor is it a substitute for the judgment of a physician, particularly in the individual case. However, do not hesitate to discuss the ASCO position and its rationale with your MO. (Note: Based on the availability of some data from prospective trials, consideration of the Recurrence Score in N1mi disease may be viewed somewhat differently from its use in other eligible node-positive patients, particularly with very low scores.)

ASCO Guideline full-text, data supplement: http://jco.ascopubs.org/content/early/2016/02/05/JCO.2015.65.2289.full

PDF Version: http://jco.ascopubs.org/content/34/10/1134.full.pdf

The use of the Oncotype test in patients with 4 or more positive nodes is not within either NCCN or ASCO guidelines. This is probably due to the magnitude of the recurrence risk such patients face, and that chemotherapy is generally recommended to such patients.

I am a layperson with no medical training, all information above should be confirmed with your MO.

BarredOwl

I had FEC before surgery and it shrank my over 6 cm mass by a 1/3. 3 large nodes st surgery but could not find and cancer in them. I was a grade 1 but I did have a ki-67 of 63 so maybe that helped shrink the cancer. I say go for all they offer you and hope you have the best outcome.... and know you did all you could.