resection of bc mets to liver prolongs survival in ER+ chemosensitive patients

Lani · 01-30-2011, 01:50 PM

from ASCO GI IN SAN FRANCISCO--Wish the study was for her2+ vs her2-, but rather it was for er+ vs er-

THE NEGATIVE:Resection of breast cancer liver metastases in patients with chemotherapy-responsive, estrogen receptor (ER)-positive primary tumors was associated with increased survival compared with resection of tumors in ER-negative primary tumors.

An ER-negative tumor and preoperative disease progression despite chemotherapy were associated with a three- to fourfold worse survival after liver metastasis resection.

THE POSITIVE:

SAN FRANCISCO -- Resection of breast cancer liver metastases paid off in a survival benefit in patients with chemotherapy-responsive, estrogen receptor (ER)-positive primary tumors, according to data from a retrospective chart review.
The chart review of more than 80 patients found those with ER-positive tumors had a median survival of 77 months with liver resection compared with 23 months for ER-negative tumors (P<0.001). An objective response to chemotherapy was associated with a median survival of 79 months versus 32 months for progressive disease as best response (P=0.049), researchers reported here at the Gastrointestinal Cancers Symposium.

In a multivariate analysis, an ER-negative tumor and preoperative disease progression were associated with a three- to fourfold worse survival after liver metastasis resection.

Although the cases were small in number, they are relevant in the context of changing views about cancer that metastasizes to the liver, said Daniel E. Abbott, MD, of the University of Texas MD Anderson Cancer Center in Houston.

"I think there has been a paradigm shift over the past 10 years or so, where it has been realized that resection of metastases from a lot of different histologic types can lead to long-term survival," Abbott told MedPage Today. "I don't think that was recognized previously. As other centers have had experience with long-term survivors, it has become more accepted."

"I think there has been something of a nihilistic attitude toward breast cancer metastasis to other organs in the past," he added.

Generally incurable, most liver metastases from breast cancer are treated with chemotherapy or hormonal therapy. However, oncologists increasingly have recognized that a subset of patients derives a substantial benefit from hepatic resection, said Abbott.

The characteristics of long-term survivors with liver metastases have remained unclear. In an effort to identify some of these traits, Abbott and colleagues reviewed medical records of breast cancer patients and found 86 patients who underwent resection of liver metastases from 1997 to 2010.

Three fourths (64 of 86) of the patients had estrogen- or progesterone receptor-positive tumors, 53 (62%) had solitary liver metastases, and 73 (85%) had liver metastases <5 cm. In addition, 65 (76%) of the patients received preoperative chemotherapy, and 10 (12%) patients received two or more chemotherapy regimens prior to resection of their liver metastases.

Defining best response as the optimal response at any time during metastatic disease, the investigators found that only two patients had progression as best response, but 19 (29%) patients had preoperative progression.

After a median follow-up of 62 months median overall and progression-free survival (PFS) were 57 and 14 months, respectively.

Univariate analysis revealed several predictors of improved or worse survival, including:

Preoperative response to chemotherapy, 79 versus 29 months, P=0.018
Preoperative progression, 23 versus 79 months, P≤0.001
Hormone receptor-negative (ER/PR-) primary tumor, 28 versus 77 months, P≤0.001
Similarly, several factors predicted PFS, including:

Objective response, 31 versus 6.4 months, P≤0.001
Stable disease, 25.3 versus 7.5 months, P=0.037
Preoperative progression, 6.4 versus 26.3 months, P<0.001
Post-hepatectomy chemotherapy, 20.7 versus 12.2 months, P=0.008
Multivariate analysis showed that an ER-negative primary tumor was associated with survival hazard of 3.3 (P=0.009) and preoperative disease progression with a hazard of 3.8 (P=0.003).

Although the review identified only a small number of cases over a 13-year period, the researchers said the findings were relevant in light of recent changes in clinical concepts about breast cancer liver metastases.

And, the findings could prove useful to physicians in discussions with patients about the possible benefits of liver resection.

"I think this information is most valuable when people are willing to counsel patients and make the tougher decisions about who should and should not have surgery and then let patients make informed decisions," said Abbott.

"If patients have a poor prognosis, they need to understand that perhaps they should not be undergoing such an invasive procedure. Conversely, people need to understand that some patients can have very long survival. Even though it's not very common, there are a select few patients with favorable biology who can benefit greatly form surgery," he added.

chrisy · 01-30-2011, 02:19 PM

Exactly, Lani! I wonder, since it was a retrospective study, if they would have the data needed to tease out the her2+ vs. her2+ question. And what the curve actually looks like. Although both questions would be difficult, as it was not a lot of patients (looks like 22 of the 86 were ER/PR-). Still, it is an important question and it's unsettling that Her2 status is not even mentioned as that is an important factor in survival - used to be bad, now its better.

These findings state that a "subset" of patients get substantial benefit (ER+). But is there a "subset" of ER-/HEr2+ that also responded well? What if only 3 of the 22 were HER2+ but all responded well?

It's really important to get that information looked at - otherwise we may be throwing out the Her2babies with the bathwater. It's likely to become even more difficult in the future to get that data if the findings from this study become standard of care and ONLY ER+ people are offered this option - most Her2+ are also ER-.

Intuitively, I think that having targeted systemic treatment (hormonal in the case of ER+, /Herceptin etc. for Her2) would be an important factor. But I want to know the facts - positive or negative - on how Her2 plays into this.

Jackie07 · 01-30-2011, 03:53 PM

Found the following link on the same report:

http://www.medpagetoday.com/MeetingC...e/ASCOGI/24490

The obvious flaw of the study is that Her2 status was not counted. As we all have learned that Her2 status has become a more favorable factor because of Herceptin/Tykerb... The 2nd question comes to mind is how many of the Er- samples are triple negative. Since a triple negative diagnosis generally has a less favorable prognosis than most of the other subsets, I have a strong feeling that it's the triple negative factor that made the Er- number turned out as such.

Joan M · 01-30-2011, 04:34 PM

I would agree about the ER/PR status. We all know that women who are ER+ do better than those who are ER-, but only as long as they take Tamoxifen or an AI. Those who don't are playing with fire. This type of study is necessary to determine whether local procedures have any benefit for women with metastatic disease. But this study was flawed.

Joan

Lori R · 01-30-2011, 05:27 PM

Lani,
Thank you so much for posting. I've been so uncertain about my continued attempts to freeze my liver met with enough surrounding margin to kill the little bugger once and for all.

I am pleased that while the stats are fuzzy regarding Her2, at least it opens the discussion about using resection for the benefit of a few.

Besides...I now have Dr. Abbott from MD Anderson on my short list for when I decide to seriously consider a liver resection.

Thank you....Lori

Sheila · 01-30-2011, 06:03 PM

This is very interesting to me as my dear friend who was diagnosed almost 4 years ago, Her2- ER+ and PR- was told today that she has reached the end of the road...she developed ascites 3 weeks ago, up until then was doing well on Navelbine, but no AI's. I think I diagnosed the ascites before her oncologist, they kept saying colon....I felt disease progression...she had a paracentesis 1 week ago, another 2 days ago and her abdiomen is already filled again. She was switched to Carbo/Gemzar, but it is playing havoc with her counts...now her Bili is going up dramatically.... her B/P is plumetting...she was discharged today from a large hospital in Chicago...I am amazed at how far she has gone down hill in 3 weeks...I just cannot lose another friend right now....I asked her why they never mentioned liver resection or ablation and she said numerous tumors...she went from working full time 3 weeks ago to this point...i am devastated any advice on what if anything I can do to help her? Her oncologist is a top onc. in Chicago at a well known hospital, and I fear she is too ill right now to seek another opinion.

chrisy · 01-30-2011, 06:46 PM

Sheila I sent you a pm. The thing you CAN definitely do is let her know how much you love her.

michka · 01-31-2011, 02:26 AM

I am going crazy. I am fighting to have my 2 liver mets taken out. I am now 20%ER+. So? On what side am I? Michka

Trish · 01-31-2011, 02:33 AM

Thanks for posting,
Trish

Missyw · 01-31-2011, 08:47 AM

Hi Lani,

I am always so grateful for your posts. I had a single met resected in June of 09. To make a very long story short, due to the location, I was not a candidate for any of the more advanced treatment options (ablation, cyberknife etc.) so resection was my only surgical option. I also went on Navelbine prior to my surgery and for a brief time thereafter. The surgery was a bit rough, but I was home in 5 days and functioning just fine. I couldn't drive for a couple of weeks. I returned to work half days after three weeks and full time after four. It is not an ideal operation, but I am still NED as of this writing, so I don't regret it at all. My onc was not thrilled with the idea, but she quickly came on board when she saw how much I wanted it. It is wonderful to have some scientific data to support the resection option. At the time, she explained her reluctance to support the surgery was because there was no data to support any additional survival time and risks were significant. Thank you again for keeping us informed of all the latest information.

michka · 01-31-2011, 09:46 AM

Thanks Lani! It gives me more courage to fight all those doctors saying it's no use for breast cancer.
My onc is trying to find a place to operate. I am sure something will work because I am pounding at so many doors.
My onc came up however with a strange chemo he intended to do after surgery. Remember he first spoke of CMF and I jumped off my chair. Now he is speaking about Endoxan and Metrotexate??? I now Endoxan because it was part of FEC I supported it so bad but not Metrotexate. What's that?
I asked why not Navelbine? He said lets get these tumors our first and we'll discuss together after. Meanwhile I am stll on Herceptin, Tykerb and Tamoxifen
Love to all. Michka

Ellie F · 01-31-2011, 10:15 AM

Hi Michka
Just wanted to clarify something. My understanding is that FEC is fluorouracil (5fu), epirubicin and cyclophosphamide.Endoxan I understand is a brand name for cyclophosphamide.
As epirubicin is an anthracycline antibiotic I was told there is a limit on how much they can use due to side effects like heart damage over a lifetime.For this reason they avoid giving it with herceptin.

Ellie

michka · 01-31-2011, 10:22 AM

Hi Ellie.Yes but isn't there anything better since FEC worked so poorly? Or does he think that since I am less ER+ he could try again? And is is better than Navelbine? That's my only question. And who takes Metrotexate? Michka

Sheila · 01-31-2011, 11:20 AM

Michka
I took Methotrexae, with Cytoxan and had a good response for 4 months, both are oral drugs, they are a Metronomic synergistic chemo, I did Herceptin at the same time....I agree though, I would try the Navelbine . Many have had a great response on it.

Ellie F · 01-31-2011, 12:37 PM

Hi Michka
I think the problem we ALL have is that as yet we do not have a sophisticated enough analysis of which drugs will work for which subsets of patients.
I agree with Sheila though that navelbine has worked well for many and is less toxic than some others.Certainly Sherry and Kim have stayed NED after having this and been maintained on herceptin.
Keeping fingers and toes crossed for a good outcome.

Ellie

DeenaH · 02-02-2011, 02:07 PM

Thank you so much for posting this! I have a tiny liver met (not confirmed, but doubled in size in 2 1/2 months), and I can't imagine why I wouldn't want to have it cut away. The liver regenerates, so what are the risks? Other than the usual risks with any surgery. I know they can't do anything until it is confirmed cancer, but if it is, I would love to either cyberknife it or resect it. This data is something I can use if I need to. I don't know why it would be more effective in ER+ vs. HER2+ though. Surgery is surgery isn't it?

Joan M · 02-02-2011, 04:23 PM

Deena,

You can have a liver resection, or a minimally invasive procedure like RFA or cryoablation.

The idea behind not doing these local procedures is that stage 4 bc is a systemic disease. If you're thinking about doing a local treatment it might be good to add chemo anyway.

Women on this board have had success with either a local treatment or chemo alone.

Joan

Lani · 02-02-2011, 11:30 PM

Deena --as I understand it the liver has the consistency of tomato aspic and, as you can guess it us hard to sew tomato aspic to tomato aspic and may be hard to stop bleeding as well.

So it may not be a walk in the park, but it is done all the time and has a good track record according to the paper I posted.

Surgery is not surgery for any tumor. Some tumors are more likely to be eradicated by cutting them out than others. Some tumors bleed more than others. Some may recruit more angiogenic factors which might wake up dormant cancer stem cells in the bone marrow than others. Some are more amenable to be removed completely without spreading other cells...

If cancer is anything,...it is complicated!!!

norkdo · 11-04-2011, 08:53 AM

Hi Michka
Just wanted to clarify something. My understanding is that FEC is fluorouracil (5fu), epirubicin and cyclophosphamide.Endoxan I understand is a brand name for cyclophosphamide.
As epirubicin is an anthracycline antibiotic I was told there is a limit on how much they can use due to side effects like heart damage over a lifetime.For this reason they avoid giving it with herceptin.

Ellie

Ellie and Mishka: Thank you a million times for this discussion/ clarification. Gold. The reason I did a search on our site for topics related to liver resection and b.c. is that I have just come from my onc who told me that if I had mets to my liver or lungs in the future that he would not recommend resection "because it does not work for breast cancer..only for colon cancer and such. BC is too systemic. If we resected your liver, tumor(s) would just pop up elsewhere." I was shocked to hear him say this and googled it. Found really positive studies (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856635/)
Really loving that Mischka's pressure changed her onc's mind. Gives me less worry for the future.
Question: after reading the link, am I correct that fifty percent of BC metastasizes?

Jackie07 · 11-04-2011, 03:10 PM

Here's an abstract on the same subject (but did not distinguish the Er status):

Updates Surg. 2010 Dec;62(3-4):143-8.
Hepatic metastases from breast cancer.

Rubino A, Doci R, Foteuh JC, Morenghi E, Fissi S, Giorgetta C, Abumalouh I, Tommaso LD, Gennari L.
Source

Department of General Surgery I, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy, arianna.rubino@humanitas.it.

Abstract

The prognosis of patients with hepatic metastasis from breast cancer treated with systemic or regional chemotherapy is disappointing. When technically feasible, liver resection offers the best results. Eighteen patients out of 22 submitted to laparotomy underwent radical liver resection. Median follow-up from liver resection was 36 months. The median time interval between breast cancer diagnosis and disease recurrence was 35 months. Median disease-free survival and overall survival from liver resection were 66 and 74 months, respectively. Median survival time from breast cancer surgery was 88.5 months. Surgical treatment of liver metastases should be carried out on young and older patients alike when site of metastases is the liver alone. Neoadjuvant treatment and preoperative diagnostic laparoscopy should be planned in future experience.