more assumptions stood on their ear: pCR after neoadjuvant treatment for her2+ breast

[Lani]

cancer may NOT indicate those with best prognosis in those that are ER+ and (on a different note) it MAY be important whether there is any remaining DCIS after neoadjuvant therapy(which happens more often in her2+ patients):

Does pCR Provide Valid Information About Long-term Outcome in Patients With HER2-Positive Disease?

Recent neoadjuvant studies support consideration of pCR as a reliable surrogate marker for long-term outcome, not only for the effect of chemotherapy but also for the effect of trastuzumab in HER2-positive breast cancer. The NOAH (NeOAdjuvant Herceptin) study demonstrated that trastuzumab in addition to chemotherapy not only doubled pCR rates compared with chemotherapy alone, but it also reduced the relapse rate by half.[5] The TECHNO (Taxol Epirubicin Cyclophosphamide(Drug information on cyclophosphamide) Herceptin Neoadjuvant) study reported a significantly more favorable disease-free and overall survival for patients who achieved a pCR compared with those who did not.[6]
However, a recent pooled analysis of the German neoadjuvant studies investigated whether the prognostic impact of pCR on long-term outcome is equal to that of neoadjuvant chemotherapy and trastuzumab for patients with hormone receptor (HR)-positive and -negative tumors.[7] In fact, whereas in 298 patients with HER2-positive/HR-negative tumors, a pCR was associated with a significantly better disease-free survival compared with no pCR (hazard ratio [HR] = 8.7, P < .001), no difference in outcome was seen in 356 patients with HER2-positive/HR-positive tumors (HR = 1.2; P = .543). Even without having an explanation for this observation, information about pCR should be used with caution in these triple-positive tumors unless other data sets provide different evidence.
Noninvasive disease as the only remaining tumor tissue (ypTis ypN0) after neoadjuvant chemotherapy is a rare event in HER2-negative disease, but it was reported much more frequently in patients with HER2-positive tumors treated with chemotherapy and anti-HER2 agents. In the GeparQuinto study, remaining noninvasive disease was found in 3.4% of HER2-negative patients, but in 14.3% of patients with HER2-positive disease after chemotherapy and trastuzumab.[8,9] Whereas earlier data sets, for example those from The University of Texas MD Anderson Cancer Center, could not indicate a different prognosis for 89 patients with remaining noninvasive disease and 199 patients with no remaining viable tumor cells (ypT0 ypN0),[10] a more recent pooled analysis of the German neoadjuvant studies demonstrated a significant higher relapse rate among 309 patients with noninvasive disease, compared with 955 patients with no remaining viable tumor cells.[2] In fact, the highest HR for disease-free and overall survival in patients with pCR vs without pCR was observed when using this most conservative definition. In clinical practice, therefore, one should not be overly optimistic in informing patients with remaining noninvasive disease about their prognosis.

[Ellie F]

Thanks Lani. This is really interesting. I did not achieve a pcr and questioned my onc about this. He said we still do not have an absolute answer as to whether this has an impact on long term survival and clinically he had seen her 2 patients relapse who had a pcr and some with large tumours and no pcr do well!
Guess bc gets more complex the more we know!
Ellie

[Rich66]

Might be enlightening to track circulating tumor cells after neoadjuvant in these groups...as well as see if hormonal therapy was delayed until after radiation.

I'd also like to see more chemo-hormonal combinations in neo/adjuvant.

The theoretical reasons for avoiding chemo-hormonal-radiation combinations have been weakening for some time.

[Debbie L.]

Isn't this pretty much in line with what we already knew about ER+ cancers in general? Somewhat of a paradox that they are much less likely to achieve a neoadjuvant PCR but that they are also less likely to recur. It's looking like it's the ER that makes the difference in this predictive PCR piece, with HER2 being irrelevant. For example, PCR seems important to prognosis for TNBC also. Right? Am I missing something more complex?

Debbie Laxague

[Lani]

Yes, you have oversimplified the implications of the findings of this research.

You definitely are not alone.

Oncologists themselves often seem to look for a cookbook simplification of
results of studies ... so that the can choose a set treatment for a set result, but as research finds breast cancer is SO much more complex than that they keep trying to hold onto guidelines (at least the Europeans seem to reexamine their guidelines at a yearly St Gallen meeting)

As with most studies, the ER status and her2 status are NOT the only differences between these patients who got neoadjuvant therapy.

The original adjuvant herceptin studies for No America were reported as showing no difference in the degree to which herceptin improved prognosis between ER+her2+s and ER-her2+s.

This adds an additional wrinkle and the article and an accompanying editorial speculate a bit about it, but the bottom line is we need to be characterizing much more than ER and her2 --there are probably several if not many types within say ER+her2+ breast cancer whose response to neoadjuvant therapy and optimal type of neoadjuvant therapy differ.

PS this is not just a study of whether ER+her2+ bc responds to neoadjuvant therapy as well as ER0-her2+ but more whether WHEN neoadjuvant therapy appears to work, whether that can be used as a surrogate for increased survival, decreased LRR

[Debbie L.]

Thanks for the clarification, Lani. Can you post a link to the full study, and to the editorial you mention? I'm curious to see the numbers, and the discussion.

Rich, I agree -- to discuss concurrent chemo and endocrine tx (not just neoadjuvantly, but that is where we might get some quick answers), we should probably start a new thread. There is really very little evidence about this, especially in the metastatic setting. And I can think of some excellent arguments for why it should work just fine.

Debbie Laxague

[Lani]

I am terrible with links here are where they articles/editorials /comments are to be found":

ONCOLOGY. Vol. 26 No. 1
Neoadjuvant Therapy for HER2-Positive Early-Stage Breast
Cancer: The Future Is Almost Here
By Hope S. Rugo, MD1 | January 17, 2012
^^^^^^^

ONCOLOGY. Vol. 26 No. 1
Improving Therapy for HER2-Positive Cancers Through
Neoadjuvant Studies
By Ian Krop, MD1 | January 17, 2012

^^^^^^^^

ONCOLOGY. Vol. 26 No. 1
.
What Is the Current Standard of Care for Anti-HER2 Neoadjuvant
Therapy in Breast Cancer?

^^^^^^^