2 different opinions on chemo regimen (ER/PR-, HER2+, LN+)

Hi, DistrictGirl,

I just saw a surgeon at a major university hospital on Wednesday. She said I would, of course, have to see the oncologist to confirm the treatment plan, but she expected it to be the Taxotere, Carboplatin, Herceptin, and Perjeta combination every 3 weeks for six months, followed by surgery (probably a lumpectomy with breast reduction), then six weeks of daily radiation and six more months of Herceptin. I'm seeing an oncologist not associated with the university this afternoon, only because the office is far more convenient, so it will be interesting to see if she recommends the same protocol.

I don't envy you the decision. Given that I have a number of other health issues going into my diagnosis, I'm debating whether to deal with the targeted / chemotherapy at all. I'll be interested in the responses you receive.

Hi DistrictGirl:

The selection of appropriate chemotherapy and HER2-targeted therapy regimens is the specific area of expertise of Medical Oncologists ("MO"), and not breast surgeons. Starting with A/C is standard in that type of regimen. So, I suspect the advice you will receive in due course from the GWU oncologist will not agree with the impressions of the breast surgeon you met there.

The reason is likely this from the NCCN guidelines for treatment of breast cancer (Version 2.2016) re neoadjuvant and adjuvant chemotherapy for early stage breast cancer:

"Trastuzumab given in combination with an anthracycline is associated with significant cardiac toxicity. Concurrent use of trastuzumab and pertuzumab with an anthracycline should be avoided."

"A/C" is doxorubicin/cyclophosphamide. Doxorubicin (also known as Adriamycin) is an "anthracyline". Hence, in this particular standard regimen for early breast cancer, the trastuzumab and pertuzumab follow A/C (are not administered concurrently with A/C).

Although there are a variety of suitable regimens available for use in the HER2-positive neoadjuvant setting, and the selection depends on many factors including risk profile, overall patient health and co-morbidities, I note that the regimen recommended to you by the MO you consulted with is one of two "Preferred regimens" among various pre-operative regimens for HER2-positive disease.

• AC followed by T + trastuzumab ± pertuzumab

(doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab ± pertuzumab, various schedules)

This includes the note: "Trastuzumab should optimally be given concurrently with paclitaxel . . . and should be given for one year total duration." (I note "paclitaxel" is also known as "Taxol".)

• TCH

(docetaxel/carboplatin/trastuzumab) ± pertuzumab

Other regimens are available and may be appropriate in the specific case.

I am a layperson with no medical training. All information above should be confirmed with a medical oncologist to ensure receipt of accurate, current, case-specific expert medical advice.

BarredOwl

Hi!

I was also diagnosed with HER2+ cancer, and I did the AC + Taxol/Herceptin/Perjeta treatment rather than TCHP. I don't know if the regimen made a difference, but my chemo wiped out all of the cancer in my breast and affected node. As a result, I opted for a lumpectomy rather than a mastectomy.

Yes, Herceptin/Perjeta are important, and I certainly got those. But, my tumor did shrink while on AC, so I don't think their absence from my regimen for two months made a difference.

My medical oncologist (MO) prefers AC + THP to TCHP because TCHP is more likely to cause gastrointestinal distress. Some women fly through TCHP with few difficulties, but others suffer from nausea, diarrhea, heartburn, etc.. Of course, those side effects can often be managed by over the counter meds; for example, Taxol gave me mild diarrhea which I managed with Immodium. But, Taxol is supposed to be the gentler cousin of Taxotere, and I often wonder how my system would have responded to the TCHP regimen. Also, one little known side effect of Taxotere is that -- in a very small percentage of patients -- it causes permanent hair loss. (I only learned about that side effect on this message board!)

Some MOs prefer TCHP because it is gentler on the heart. Both AC and Herceptin can cause heart issues. If you go the AC + THP route, your MO should monitor your heart very carefully. I got MUGAs (heart scans) every three months while I was doing AC +THP, and during my year of Herceptin.

In short, choice of chemo regimen may vary by oncologist and his/her preferences. My MO wants her patients to finish chemo, and she felt like too many of her patients were quitting on TCHP before they completed all six infusions. Good luck!

Hi District Girl,

I was treated at a major cancer center and had the first regimen you describe. However, I had surgery before starting chemo. I also had H and P adjuvantly. Good luck to you whatever you decide. I could be mistaken but carbo seen more frequently in triple negative and BRCA+ cancers, but perhaps this is splitting hairs. All the chemo you wrote about above work

Hi DistrictGirl:

Ruminating further, factors like your relatively young age (30) and ER/PR status might also be considerations in the choice of regimen. Are both tumors known to be ER- and PR-negative? Just some more fodder for discussion with your team.

BarredOwl

Hi hoosier238:

Do you happen to have a link to a summary or publication that reported the finding in item (2)? I am wondering if there was a subgroup analysis for "triple-positive" versus HER2+ only (hormone receptor-negative).

BarredOwl

Thanks hoosier238. I took a look at the 2014 Lancet paper at the link. It describes the results of the "Neo-tAnGo" trial. The regimens tested were:

(a) epirubicin (E) and cyclophosphamide (C) then paclitaxel (with or without gemcitabine);

(b) paclitaxel (with or without gemcitabine) then epirubicin (E) and cyclophosphamide (C)

Epirubicin (E) is an "anthracycline", but this is an "EC"-containing regimen, as distinct from "A/C" (where "A" is Doxorubicin, also known as Adriamycin).

Importantly, in this study, patients "with HER2-positive disease did not receive neoadjuvant trastuzumab, but only received adjuvant trastuzumab according to local protocols."

Subgroup analysis showed differing results in the ER+HER2+ versus ER-HER2+ subsets, although the subsets were too small to draw any conclusion.

Thus, the Neo-tAnGo study only tested the neoadjvuant sequencing of "EC" with paclitaxel. Herceptin (trastuzumab) was not given neoadjuvantly, but only following surgery. Thus, the study does not appear to address the question of the preferred sequencing of trastuzumab in the neoadjuvant setting with any agent, or the preferred sequencing of neoadjuvant "A/C" (doxorubicin / cyclophosphamide), trastuzumab and taxanes.

The discussion section of the paper refers to a variety of studies relating to epirubicin ("E")-containing regimens, including the Z1040-Alliance neoadjuvant study which looked at FEC, paclitaxel and trastuzumab regimens. The available evidence apparently has led to the incorporation of both sequences of "FEC"-containing regimens in the NCCN guidelines (Version 2.2016) under "Other regimens" for HER2-positive early breast cancer:

• FEC followed by docetaxel + trastuzumab + pertuzumab

• FEC followed by paclitaxel + trastuzumab + pertuzumab

• Pertuzumab + trastuzumab + docetaxel followed by FEC

• Pertuzumab + trastuzumab + paclitaxel followed by FEC . . . .

[See NCCN guidelines for a complete list of "Other regimens"]

In contrast, with the "A/C" regimen discussed above, only the AC-first sequence is included in the NCCN guideline at this time (as a preferred regimen) for neoadjuvant treatment of HER2-positive early stage breast cancer.

I note that guidelines are by nature snap-shots in time, do not mandate individual treatment, and more recent studies may be available that influence treatment recommendations received today. In a rapidly evolving field with a large body of literature, it is important to consult an expert oncologist who stays current with recent clinical developments to obtain the most up to date information about regimen choice and the quality of the available evidence.

I am a layperson only, all information above should be confirmed with a medical oncologist.

BarredOwl

Sending good vibes your way for productive and informative appointments!

BarredOwl