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Pathologic Complete Response (pCR) on Prognosis

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Topic: Pathologic Complete Response (pCR) on Prognosis
Posted By: 123Donna
Subject: Pathologic Complete Response (pCR) on Prognosis
Date Posted: May 01 2012 at 10:37am
Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes
Purpose The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain.

Methods Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane–based chemotherapy in seven randomized trials were analyzed.

Results Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) –positive (P = .013), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis.

Conclusion pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

http://jco.ascopubs.org/content/early/2012/04/11/JCO.2011.38.8595.abstract - http://jco.ascopubs.org/content/early/2012/04/11/JCO.2011.38.8595.abstract





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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




Replies:
Posted By: CatWhispurrer
Date Posted: May 13 2012 at 11:45am
Donna - what does luminal A and luminal B mean?   I see it must be a sub-type but does anyone ever get tested for these subtypes?    How would we know if we have this subtype?  I have never heard the term luminal A or B before.

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Found lump 9/16/11, age 55, Diagnosed 10/27 IDC TN, LX/SNB 12/7/11, Stage 1, Grade 3, 1.8 cm, 0/3 nodes, BRCA-, DD A/C on 1/23/12, followed by DD Taxol. 3/14/14 Stage IV, 3/26/14 Paclitaxel


Posted By: dmwolf
Date Posted: May 14 2012 at 8:16pm
Luminal A, Luminal B, Basal, ERBB2, and Normal subtypes are all classifications of breast cancer derived from gene expression studies.  They are called 'intrinsic subtypes', and are similar but not identical to subtyping using receptors like ER and PGR and HER2 by IHC or FISH.    Luminal A cancers tend to be ER positive (estrogen receptor), HER2 negative, and with a low proliferation (Ki67) rate.  Luminal B cancers are usually ER positive as well, but can also have positive HER2 status and are likely to have higher proliferation.    They are the more aggressive subset of ER+ cancers.    Most TNs are Basal, though some are distributed among the other subtypes.  

I hope that helps!
d



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DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.


Posted By: dmwolf
Date Posted: May 14 2012 at 8:18pm
One final note:  currently there is no treatment consequence to belonging to one subtype over another, except for LumA's generally not needing chemotherapy.


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DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.


Posted By: 123Donna
Date Posted: Sep 25 2012 at 9:24pm

Triple-negative breast cancer (TNBC) and residual disease (non-pCR): Does size matter?


http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=125&abstractID=103238 - http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=125&abstractID=103238


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: debB
Date Posted: Sep 25 2012 at 10:22pm
Donna,

Thanks for posting this. I read this several days ago and was very happy to read the conclusion that size does matter. Everything up to this point has been black and white; complete response or not, good prognosis or not, and no grey area. It is nice to know that some shade of grey does exist. I do hope that they also go back and analyze the data with the node status to see if that makes any differnce.

Is seems like there has been some encouraging news this past week!
Deb

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Dx 4/29/11, 46 yrs old, 3.9 cm tumor, Stg 2 Grade 3 chemo 4 rounds DD AC, 12 weekly taxol, finish. Lumpectomy, 2mm residual tumor. 37 rounds rads completed. Cisplatin/PARP trial


Posted By: mindy555
Date Posted: Sep 30 2012 at 12:27am
This is precisely what my MO was trying to explain to me.   Having seen the aggressiveness of some stage I tumors,  we ultimately came to the conclusion biology trumps all.  However, according to my onc. size plays a highly significant role.  

My own post BMX path was held up due to possible in situ cells.  The end conclusion was there were none and pathology was clear.   I'm hoping this is the case and they didn't lose the specimen.   I too hope node status is studied more in-depth.

Thanks for posting Donna and hope you're doing well Deb.


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Dx July 2011 56 yo
Stage I IDC,TN,Grade 3
Grew to Stage IIa- No ev of node involve- BRCA1+ chondroid metaplasia
Daughter also BRCA1+
Mass grew on Taxol
FEC 6x better
BMX 3/19/12 pCR NED
BSO 6/2012


Posted By: 123Donna
Date Posted: Sep 02 2014 at 11:11pm
Subtype, pCR Predict Locoregional Recurrence Following Neoadjuvant Therapy 

http://www.onclive.com/conference-coverage/BCS-2014/Subtype-pCR-Predict-Locoregional-Recurrence-Following-Neoadjuvant-Therapy" rel="nofollow - http://www.onclive.com/conference-coverage/BCS-2014/Subtype-pCR-Predict-Locoregional-Recurrence-Following-Neoadjuvant-Therapy


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: mindy555
Date Posted: Sep 03 2014 at 7:43pm
Here's another link to get to a PDF which squelches pCR being an independent prognosis marker- with other factors influencing TNBC outcomes.

Hope this works Wacko

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCAQFjAA&url=http%3A%2F%2Fwww.clinical-breast-cancer.com%2Farticle%2FS1526-8209%2812%2900217-0%2Fpdf&ei=hYgHVKPCKsSujALm6oDIDw&usg=AFQjCNENHxaZMmTz0hTGIvEVUTnMPzl9nw&bvm=bv.74115972,d.cGE" rel="nofollow - http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCAQFjAA&url=http%3A%2F%2Fwww.clinical-breast-cancer.com%2Farticle%2FS1526-8209%2812%2900217-0%2Fpdf&ei=hYgHVKPCKsSujALm6oDIDw&usg=AFQjCNENHxaZMmTz0hTGIvEVUTnMPzl9nw&bvm=bv.74115972,d.cGE

Smaller study on Prognostic Factors for 3N Patients Receiving Preoperative Systemic Therapy from 2013.


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Dx July 2011 56 yo
Stage I IDC,TN,Grade 3
Grew to Stage IIa- No ev of node involve- BRCA1+ chondroid metaplasia
Daughter also BRCA1+
Mass grew on Taxol
FEC 6x better
BMX 3/19/12 pCR NED
BSO 6/2012


Posted By: 123Donna
Date Posted: Oct 18 2014 at 12:54pm
How New FDA Flexibility In Breast Cancer Trials Can Help High Risk Patients

http://www.biopharmadive.com/news/how-new-fda-flexibility-in-breast-cancer-trials-can-help-high-risk-patients/322359/" rel="nofollow - http://www.biopharmadive.com/news/how-new-fda-flexibility-in-breast-cancer-trials-can-help-high-risk-patients/322359/




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 22 2014 at 9:40pm
http://www.onclive.com/publications/Oncology-live/2014/November-2014/Expert-Says-pCR-Data-Support-Neoadjuvant-Therapy-in-HER2-Positive-Breast-Cancer" rel="nofollow - http://www.onclive.com/publications/Oncology-live/2014/November-2014/Expert-Says-pCR-Data-Support-Neoadjuvant-Therapy-in-HER2-Positive-Breast-Cancer

Holmes said the CTNeoBC meta-analysis2 showed that achieving pCR following preoperative chemotherapy was an especially strong predictor of event-free survival in aggressive forms of breast cancer. Attaining pCR reduced the risk of death by 92% in cancers that were HER2-positive and hormone receptor–negative cancers and by 84% in triple-negative breast cancers (TNBCs). - See more at: http://www.onclive.com/publications/Oncology-live/2014/November-2014/Expert-Says-pCR-Data-Support-Neoadjuvant-Therapy-in-HER2-Positive-Breast-Cancer#sthash.DZsgo6EU.dpuf


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 30 2015 at 12:40pm
Axillary pathologic complete response linked to longer survival in breast cancer
Axillary pathologic complete response appeared associated with improved 10-year RFS and OS in patients with breast cancer who had cytologically confirmed axillary lymph node metastases, according to the results of a retrospective study.

". . .They retrospectively reviewed medical records of women diagnosed with stage II to stage III breast cancer with axillary lymph node metastases. All study participants received primary systemic chemotherapy between 1987 and 2007 at MD Anderson Cancer Center.

Researchers stratified women by axillary status after primary systemic chemotherapy and estimated survival outcomes according to response in the breast and axilla.

OS and RFS served as primary endpoints.

The analysis included data from 1,600 women (median age at diagnosis, 49 years; range, 21-86), of whom 454 (28.4%) achieved axillary pathologic complete response.

Women who achieved axillary pathologic complete response appeared more likely to have HER-2–positive or triple-negative breast cancer (< .001), pathologic complete response in the breast (< .001), high-grade tumors (< .001), and lower clinical and pathologic T stage (= .002).

Compared with patients who had residual axillary disease, patients with axillary pathologic complete response appeared more likely to achieve 10-year OS (84% vs. 57%; < .001) and RFS (79% vs. 50%; < .001).

Among patients with axillary pathologic complete response, 10-year OS was higher among those with pathologic complete response in the breast (90% vs. 72%; < .001).

Among patients with residual axillary disease, those who achieved pathologic complete response in the breast achieved better 10-year OS (66% vs. 56%; = .02). . . "

To read the entire article:

http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7Baf25341d-0e0e-4987-90cd-dddc0980999c%7D/axillary-pathologic-complete-response-linked-to-longer-survival-in-breast-cancer" rel="nofollow - http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7Baf25341d-0e0e-4987-90cd-dddc0980999c%7D/axillary-pathologic-complete-response-linked-to-longer-survival-in-breast-cancer



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jan 12 2019 at 11:39am

SABCS 2018: Meta-analysis of Pathologic Complete Response and Outcomes in Breast Cancer

Overall, patients with breast cancer who had a pathologic complete response were 69% less likely to have a disease recurrence compared with those who did not have a pathologic complete response. The relationship was strongest among patients with triple-negative or HER2-positive breast cancer with a pathologic complete response, where such patients were 82% and 68% less likely, respectively, to have disease recurrence.

Key Points

  • Patients with breast cancer who had a pathologic complete response were 69% less likely to have disease recurrence compared with those who did not have a pathologic complete response. The relationship was strongest among patients with triple-negative or HER2-positive breast cancer with a pathologic complete response, where such patients were 82% and 68% less likely, respectively, to have a disease recurrence.
  • Patients with a pathologic complete response also had a 78% lower risk for mortality compared with those who did not have pathologic complete response overall.
  • The association of pathologic complete response with reduced recurrence was comparable between patients who received adjuvant chemotherapy (66% less likely to have recurrence) and those who did not receive adjuvant chemotherapy (64% less likely to have recurrence).

To read the entire article:

http://www.ascopost.com/News/59546" rel="nofollow - http://www.ascopost.com/News/59546




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: MikeW
Date Posted: Jan 17 2019 at 11:09pm
Interesting but what stage were they talking about? My wife is Stage 4 TNBC but recently had 2, 3 month apart, clear PET scans. She got NED on Halaven, after Xeloda and AC failed her.


Posted By: 123Donna
Date Posted: Jan 18 2019 at 11:17am
MikeW,

The discussion is about the initial diagnosis and for women who have neoadjuvant chemo prior to surgery.  I'm assuming it would be women initially diagnosed with Stage 0 - 3 breast cancer.  I guess it could include Stage 4 too if the neoadjuvant therapy shows a complete response at the time of surgery.

"Pathologic complete response after neoadjuvant chemotherapy was associated with a significantly lower recurrence risk and higher overall survival in patients with breast cancer, and pathologic complete response after neoadjuvant chemotherapy had a similar association with improved outcomes among those who received adjuvant chemotherapy vs those who did not, according to meta-analyses of data from 52 clinical trials presented by Spring et al at the 2018 San Antonio Breast Cancer Symposium ( https://www.abstracts2view.com/sabcs18/view.php?nu=SABCS18L_1698&terms=" rel="nofollow - Abstract GS2-03 ).

A pathologic complete response was defined as the lack of all signs of invasive cancer in the breast tissue and lymph nodes removed during surgery after treatment with chemotherapy."


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




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