UK study describes poor prognosis of small her2+ tumors, recommnds widening herceptih

[Lani]

use guidelines in UK/ or at least chemotherapy guidelines. These patients had been treated with tamoxifen alone--graph in article showed 65% 5,10,15 year survival for small her2+ tumors treated without chemotherapy or herceptin, ie if one made it out 5 years one is probably going to do well.

Will look at this survival curve again, but it spoke volumes.

Hope this helps the UK guidelines catch up to those in North America

Clinical Study
British Journal of Cancer (2009) 100, 680–683. doi:10.1038/sj.bjc.6604940 www.bjcancer.com
Published online 17 February 2009
Poor survival outcomes in HER2-positive breast cancer patients with low-grade, node-negative tumours

http://www.nature.com/bjc/journal/v1...f/6604940a.pdf

S M Tovey1, S Brown1, J C Doughty1, E A Mallon1, T G Cooke1 and J Edwards1

1Glasgow Royal Infirmary, Section of Surgery, Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, Level 2, Queen Elizabeth Building, 10 Alexandra Parade, Glasgow G31 2ER, UK

Correspondence: SM Tovey, E-mail: smtovey@doctors.org.uk

Received 31 October 2008; Revised 20 January 2009; Accepted 20 January 2009; Published online 17 February 2009.

Top of page
Abstract
We present a retrospective analysis on a cohort of low-grade, node-negative patients showing that human epidermal growth factor receptor 2 (HER2) status significantly affects the survival in this otherwise very good prognostic group. Our results provide support for the use of adjuvant trastuzumab in patients who are typically classified as having very good prognosis, not routinely offered standard chemotherapy, and who as such do not fit current UK prescribing guidelines for trastuzumab.

[Christine MH-UK]

The article should be useful, too, for her2+ patients everywhere who wonder whether their cancer is likely to need chemo and herceptin.

I think this sentence merits repeating:
"Our results suggest that no HER2-positive patient should be classified as at ‘low risk’."

Glad to see CRUK doing something worthwhile, since it is a charity I support.

Best wishes,

Christine

[RobinP]

Let me just remind everyone too, that the study didn't even evaluate her2 positives that were 1.0cm or smaller due to too small of study size. So What does this study say about the smallest of her2 tumors 1cm or under-NOTHING.

[Jean]

As always thanks Lani,

Found this informative article from Medscape.




SABCS 2008: All HER2-Positive Tumors Need Adjuvant Treatment


Nick Mulcahy

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Assess clinically focused product information on Medscape.
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December 15, 2008 (San Antonio, Texas) — Currently, small and low-grade HER2-positive tumors do not typically receive adjuvant systemic therapy. However, 2 new studies presented here at the 31st Annual San Antonio Breast Cancer Symposium suggest that they should.
"The biology of the tumor, and not the size or grade, matters most in these patients," said Sian Tovey, MD, from the Glasgow Royal Infirmary, in Scotland, about the 2 studies. "No HER2-positive patient should be considered low risk," she added.
No HER2-positive patient should be considered low risk. Dr. Tovey presented a study on low-grade HER2-positive tumors at the meeting, which shows that patients with the low-grade tumors have a poor prognosis. The results of this study, and another study that shows that small HER2-positive tumors have an increased risk for recurrence, are both practice changing, said Dr. Tovey. "Practice is already changing in Glasgow [because of] both of these results," she said.
The needed change is simple, she suggested. "Any patient who is HER2 positive should be categorized as high-risk and should receive adjuvant trastuzumab therapy."
In the second study, Ana M. Gonzalez-Angulo, MD from the University of Texas MD Anderson Cancer Center, in Houston, said that their new data also challenge the current approach to HER2-positive patients. In that study, patients with tumors 1 cm or smaller had a significant risk for relapse, compared with other tumor types. "The current guidelines call for no further therapy if the tumors are less than 5 mm or [to] consider therapy if the tumors are from 6 to 10 mm, but these data challenge that thinking and show that this group of women may benefit from additional therapy," said Dr. Gonzalez-Angulo.
Drs. Tovey and Gonzalez-Angulo and their respective colleagues called for clinical trials to assess adjuvant therapy in these patients.
Small Tumors But Increased Risk for Recurrence
The study presented by Dr. Gonzalez-Angulo was a retrospective analysis of 965 patients from the MD Anderson Cancer Center diagnosed with breast cancer between 1990 and 2003. The median age of the patients at diagnosis was 57 years. All tumors were 1 cm or smaller, and the cancers were node-negative. Most of the tumors (68%) were hormone-receptor positive, but 10% were HER2 positive and 23% were triple-receptor negative.
The 5-year recurrence-free survival was 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively. The 5-year distant recurrence-free survival was 86.4% and 97.2% in the 2 patient groups. Thus, patients with HER2-positive tumors had a 2.68 times greater risk for recurrence and a 5.3 times higher risk for distant recurrence than those with HER2-negative tumors. HER2 positivity is a powerful negative prognostic factor for patients with tumors 1 cm or less, noted Dr. Gonzalez-Angulo.
"This paper shows that patients with HER2-positive tumors 1 cm or less have a significant risk of relapse and should be considered for clinical trials of systemic anti-HER2 adjuvant therapy or, if a clinical trial is not available, adjuvant therapy should be discussed with them," summarized Dr. Gonzalez-Angulo.
Low-Grade Tumors But Poor Prognosis
In the other study, Dr. Tovey and her Scottish colleagues retrospectively analyzed women with low-grade node-negative HER2-positive tumors. These tumors are typically not treated with adjuvant therapy and are seen as low risk, she noted.
The cohort of 367 early breast cancer patients with grade 1 or 2 cancers were diagnosed between 1980 and 2002 and had a median follow-up 6.2 years. The cohort was analyzed to assess the impact of HER2 status on survival. A total of 123 patients in the cohort (12.9%) were HER2 positive.
The overall hazard ratio for HER2 positivity was 6.78, with 5-year breast-cancer-specific survival rates for HER2-negative patients of 96%, compared with only 68% for the HER2-positive patients. The reduction in survival in HER2-positive cases persisted when patients were split into subgroups by estrogen-receptor status, tumor size, and age.
The Scottish study also reviewed all early cases of HER2-positive early breast cancer to determine what percentage of patients received adjuvant therapy. Only 50% of the HER2-positive early breast cancer patients received trastuzumab therapy in 2006. The most common reason for not receiving trastuzumab was low-risk status precluding chemotherapy.
"The substantial reduction in survival shown in our retrospective cohort provides support for the use of trastuzumab in these 'low-risk' HER2-positive patients who typically are classified as [having a] very good prognosis, are not routinely offered standard chemotherapy and, as such, do not fit current prescribing guidelines for trastuzumab," noted Dr. Tovey and colleagues from the Royal Glasgow Infirmary in their poster presentation.
The researchers have disclosed no relevant financial relationships.
31st Annual San Antonio Breast Cancer Symposium (SABCS): Abstracts 701 and 702. Presented December 12, 2008.



PLEASE NOTE:
In the second study, Ana M. Gonzalez-Angulo, MD from the University of Texas MD Anderson Cancer Center, in Houston, said that their new data also challenge the current approach to HER2-positive patients. In that study, patients with tumors 1 cm or smaller had a significant risk for relapse, compared with other tumor types. "The current guidelines call for no further therapy if the tumors are less than 5 mm or [to] consider therapy if the tumors are from 6 to 10 mm, but these data challenge that thinking and show that this group of women may benefit from additional therapy," said Dr. Gonzalez-Angulo.

[MJo]

Dang! I'm glad my doctor and I agreed to hit my small tumor with every weapon in the 2006 arsenal. These studies remind me to live as fully as possible and to be grateful for every day I've got.

[Hopeful]

"In conclusion, these results, in the context of other recently reported retrospective studies and adjuvant trials, provide support for the rationale of using adjuvant trastuzumab in this subgroup of patients, who are typically classified as having very good prognosis . . . A clinical trial to assess the benefit of adjuvant trastuzumab within this group of HER2 patients would resolve this. Whether trastuzumab would be effective alone in these patients (without the potential side effects of standard chemotherapy regimes) deserves investigation. The combination of hormonal therapy and trastuzumab may be particularly beneficial in ER-positive patients, because trastuzumab may overcome the crosstalk between HER and ER receptors, which is likely responsible for the reduced efficacy of hormonal therapy in this group."

Hopeful

[karen z]

Lani,
Thanks much for the post.
karen z

[Jean]

Hopeful,
Very true remarks regarding trials /or/studies for subtypes and herceptin. I have not found any information in this area.

I was hoping that some data had been pusblished
certainly the information has been collected regarding
er positive/er negative and herecptin. We now only have one lump sum of subtypes.

I have been curious for a long time as to this thought.
Length of time of treatment depending on subtype?

Regards,
jean

[schoolteacher]

Hopeful,

Thank you for pointing this out:

"The combination of hormonal therapy and trastuzumab may be particularly beneficial in ER-positive patients, because trastuzumab may overcome the crosstalk between HER and ER receptors, which is likely responsible for the reduced efficacy of hormonal therapy in this group."

I needed some more positive information today, and this helped a lot.

Amelia

[hutchibk]

Interesting timing of a UK study about Herceptin use...

NICE just decreed no Herceptin approval for advanced Her2 patients who have mets show up beyond CNS (ummm, it doesn't cross the BBB, so why would they approve it for advanced CNS treatment, but not bone or organ involvement?) Apparently, anyone currently being treated for mets that are not CNS will be discontinued.

[karen z]

hutchibk,
can you send along a link to the information you are referring to or tell us a way to find? thanks.
kz

[hutchibk]

Read this posting http://www.her2support.org/vbulletin...ad.php?t=38277
and contact some of our UK ladies directly... they have the info first hand.I haven't found back-up articles yet about the Herceptin claim mentioned above... but it appeared in the above thread from the Herceptin/Tykerb forum, as well as yesterday on the BCA forums:
http://bca.ns.ca/forum/showthread.php?t=33725


and the Tykerb denial is here:
http://www.google.com/hostednews/ukp...smyZaidpPI3EFA
and here:
http://www.channel4.com/news/article...d+drug/3013382

and this sad news about Ann Marie Rogers: http://www.independent.co.uk/life-st...r-1638500.html

You will find a n umber of PDF documents on the NICE web site here where it documents what will happen for advanced breast cancer care in the UK.

[karen z]

Thanks unregistered- got it.
kz

[Debbie L.]

It looks to me like this is not about SMALL tumors so much as it is about low grade (and node negative ones). We do already know that it's less tumor size and more other measurements of aggressiveness, but usually grade is relevant in that theory. Low grade HER2 tumors are hard to find, and they didn't find many. In addition, they admit that their HER2+ group had more grade 2 (vs. grade 1 - they didn't include any grade 3's) and also more ER- than ER+ (compared to the HER2- cohort). Plus, they admit that this was an extremely small study (n=22). I'm not a statistician but if they were able to achieve significance with that few cases, I think that it does point to a big difference.

It's puzzling that they found such a huge hazard ratio. Most discussions of HER2+'s significance (pre-Herceptin) that I've seen put it in the 1.5 to 2 range. I just checked Adjuvant! and it still does not have the new version that's supposed to include HER2 but the discussion still says he thinks it's in the range of 1.5.

I need to find the transcripts to the bcupdate series that I've been listening to. Recently, some expert-or-other (sigh, the memory) said that he feels there is a subset of low risk triple positives who have a very good prognosis even without Herceptin. I'm sorry - I can't even remember if he was citing a study or simple expressing a personal opinion. Does anyone else remember this discussion?

My guess is that there may be a small subset of low risk HER+ tumors but that we haven't yet figured out how to know who they are. When we do, I suspect (like my above unnamed expert) that it will be about high ERPR (like >90%). I'm wondering if assays like oncotype that give us a quantitative ERPR will help sort this out.

Debbie Laxague

[Debbie L.]

I read this a little differently. They didn't quite say that they wouldn't use Herceptin for mets - they said they would discontinue it after progression. So for the ones who get those amazing forever-responses right off the bat - they'll stay on Herceptin. But the way I read it, when they switch chemo because of progression (and I only saw 4 chemo choices), then they discontinue the Herceptin. That is not common practice here and there is at least one study from SABCS 2008 showing the benefit of continuing Herceptin when switching chemo (because of progression). Although it is true that there isn't much evidence, even though most oncs agree that continuing Herceptin is of benefit.

Also - apparently there is not the array of radiation choices that we have here for brain mets? They only talk of WBR. Even after surgical resection of single brain mets, they recommend WBR. I wonder if that recommendation comes from lack of technology, or from cost considerations? I wonder what the cost savings is - you'd think multiple sessions of WBR would cost more than the targeted radiations of shorter duration but maybe it's the cost of such specialized equipment? I wonder if they have disclosed how they came to these decisions. But I don't have time to look right now.

Debbie Laxague

[lizm100]

Microinvasive breast cancer (Tmic): A descriptive mono-institutional report.

Sub-category:

Local-Regional Therapy

Category:

Breast Cancer--Local-Regional and Adjuvant Therapy

Meeting:

2008 ASCO Annual Meeting

Printer Friendly

E-Mail Article

Abstract No:

11508

Citation:

J Clin Oncol 26: 2008 (May 20 suppl; abstr 11508)

Author(s):

A. Ferro, A. Caldara, R. Triolo, M. Barbareschi, E. Leonardi, O. Caffo, M. Pellegrini, M. Frisinghelli, D. Bernardi, E. Galligioni

Abstract:

Background: Tmic is considered a separate pathologic entity with good prognosis, but its clinical significance and management remain controversial. We present our retrospective review of 69 cases of Tmic, among 6,023 BC pts (1%), observed at our institution from 1990 to 2007. Methods: We considered Tmic a single focus of invasive carcinoma < 2 mm or up to 3 foci < 1 mm in greatest dimensions (according to Silver and Tavassoli, Cancer 1998). Descriptive analysis of pts characteristics, treatment and clinical outcome are reported. Results: Among 69 women (mostly asymptomatic, presenting mammographic abnormalities, with median age 52, range 20-78), T< 1 mm in 55 pts (80%) and T< 2 mm in 14 (20%) were observed. Radical mastectomy was performed in 31 pts (45%) due to extended in situ component or multicentric disease, and breast conserving surgery (BCS) in 38 (55%). All pts but 4, received axillary node dissection (61 pts) or sentinel node biopsy (4 pts), with only 1 N+ pt. The "in situ" component presented ductal in 91% and lobular histology in 9% of the cases, with predominant comedo subtype in 45%. All Tmic presented ductal histology with positive hormone receptor status (HR) in 45%, negative in 22% and unknown in 33%. Among 32 HER-2 evaluable pts, HER-2 was overexpressed in 34% and normal in 66%. Adjuvant treatment consisted of radiotherapy in 87% of BCS pts, chemotherapy in 5 HR neg pts, endocrine therapy in 7 and chemo-endocrine in 1 N+ pt. At a median follow-up of 93 months RFS and BC specific OS were 91 and 100%, respectively. Three pts experienced a local relapse (2 DCIS and 1 invasive) and 1 distant metastases (bone). None of relapsed pts had received systemic adjuvant therapy. Three pts died for non-breast cancer causes. Six pts developed a controlateral BC (9%): none of them progressed or died of disease. Conclusions: Our data appear in large part comparable to those of the literature on Tmic and, in our experience, the inclusion of microinvasion > 1 mm and < 2 mm did not change the good prognosis of microinvasive cancer.


Since everyone else is posting their finds, I thought that I would post what I found on the ASCO website.

The decision to terminate Herceptin treatment is clear in the guidelines from NICE

For patients who are receiving treatment with trastuzumab for advanced breast cancer, discontinue treatment with trastuzumab at the time of disease progression outside the central nervous system. Do not discontinue trastuzumab if disease progression is within the central nervous system alone.

As I read this it means that you only get Herceptin if your cancer is in the brain or spinal cord, otherwise you stop treatment immediately.

Also the new guidelines for early stage breast cancer state that you only get Herceptin for 1 year or when the disease recurs which ever is the sooner.

As to WBR yes its technology as the UK has only one Cyberknife (recently installed I believe) and its in a prvate hospital, not normally available to NHS patients.

[Debbie L.]

It says "at time of disease progression" it is to be stopped. Disease progression in this context doesn't mean initial diagnosis of mets, it means progression during treatment for mets. So basically, first round treatment at stage IV diagnosis gets Herceptin plus whatever, but it's discontinued at disease progression.

Some women could stay on it forever (those amazing first and lasting responses). Others might get it only briefly if they have to change chemo or hormonal tx - those are the ones that would be treated much differently in the US. It doesn't say discontinue immediately for those who are stable. If you're on Herceptin and stable, then you stay on Herceptin, regardless of CNS vs. elsewhere. At least that's how I read it. I'm not defending this approach, I'm just saying that's how I read it. Other interpretations from the rest of ya'll?

Debbie

[Lani]

Let's say 20-25% are her2+, which is the case in macroinvasive breast cancer but may not be the case in microinvasive breast cancer (it is NOT the case in DCIS), that would make 14-17 patents about have of which 7-8, let's say, would be her2+ER+ vs her2+ ER- if distributed in the same proportions as macroinvasive breast cancer ie, IDC (usually although some invasive her2+ breast cancers have different microscopic histologies ie, inflammatory etc)

Doesn't sound like this study would be able to draw conclusions with statistical significance either.