Any one else a Stage 1 AND Grade 1 Her2++++?

[swimangel72]

Am I the only one? My oncologist originally acted shocked when my FISH report came back Her2+++, so shocked he sent it out again for a second FISH at a different lab, and this one came back even higher at Her2++++ (4.5). I didn't truly understand why he was so surprised - but now that Ive been on the internet researching so much, I haven't seen anyone else like me, that is Her2+ but only a Grade 1. My tumor was highly ER+ and PR+ (both 90%) but two different path reports said it was "well differentiated". My Oncotype DX score was 22.........so I guess my question is, does your Her2+ status CHANGE your Grade status? Or are they totally independent?
I still worry that my onc put me on Navelbine for 4 months instead of the usual course of chemo with Herceptin for a year (I'll be done with the Herceptin in April). Even though I had the mastectomy - I still worry that when the Herceptin tx is finished, I'll get a recurrence or mets........which is a worry we all share I know.

[CindyE]

I'm stage 1 and grade 1 too. I don't know a lot about all my path reports but for sure am highly her2+. I'll be done with Herceptin in May. I too worry about a recurrence. I will continue to pray for you and remember you when I first joined this forum. Take care and God bless.

[suzan w]

as you can see by my signature, I was also stage 1, her2+++, and ER+. At the time herceptin was not standard treatment for early stage bc. I received herceptin "off lable" and 1/2 was through my treatment, the FDA approved herceptin for early stage. I do believe that stage 1, her2+++ is not real 'common' but there are several of us here at this site!

[AbbyDawg]

Hi!

I was Stage 1 (no + lymph nodes) - Grade 3 agressive IDC and DCIS and Her2+. Double mastectomy 6/1/2006 then 4x dd A/C. I got my Her2+ results too late for Herceptin. Was also in TEACH trial for 9 months - took 1500mg Tykerb (Lapatinib) daily. Am on Arimidex.

[Lani]

I think the others are referring to being both grade I AND stage I. Stage I refers to the size , grade I to the appearance under the microscope, particularly the degree of differentiation of the cells. I can't quote you numbers right off the bat, but in the papers I read grade I is rare in her2 amplified breast cancer, but not impossible.

Stage I however is not THAT rare in her2s (probably just means it was caught earlier by mammogram, etc before it got to a larger size) According to the latest paper given at this year's San Antonio conference, the additional agressiveness conferred on a 1 cm or less tumor by being her2 amplified warrants treatment with herceptin because of the worse 5 year survival figures associated with her2 positivity, even in those tumors less than 1 cm. None of you specified the exact size of your stage I tumors-- Stage is usually listed as 1a, 1b, 1c etc so it is unclear whether your tumors fell into that <1 cm group. Over 1 cm the advantage of herceptin treatment was even more obvious.

It appears they haven't yet determined whether size/grade or biologic behavior determined by which pathways are activated are the predominant factor driving prognosis. Usually grades end up to be correlated with the predominant pathway eg her2 and often size as well (the more aggressive the tumor the more likely it will larger and more extensive when discovered , but again, mammography may be allowing more of these lesions to be caught earlier so they need not be larger. Also the lesions tend to be of a higher stage ie larger on average for more agressive tumors such as her2 + ones, but that is on average and doesn't hold for any one person's tumor.

If I find a paper covering this particular issue I will try to post it, but few her2 amplified tumors are grade I so I might be looking for quite a while.

By the way, did you think of get a second pathologic opinion regarding the grade? You can do so by having your slides submitted to another facility's pathology department and from what I have seen,charges are usually relatively reasonable, especially if it is unnecessary to repeat the FISH testing or do any additional immunohistochemical testing.

MD Anderson, Mayo Clinic and Stanford offer the service and I would suspect Memorial Sloane Kettering, Dana Farber and Johns Hopkins would as well.

Hope some of this helped.

[swimangel72]

Thank you for your prayers Cindy - hope your Herceptin tx's are going well. My last muga score dropped by only 4 percentage points from a 67% to a 63% for which I'm relieved!

Suzan I'm glad you were able to get Herceptin - I'm also on Arimidex. Do they think your osteoporosis was caused by the Arimidex? My onc told me it's a real issue - so I'm trying to increase my calcium.

Abby I love your dog - is she a collie? We're a cat family - I'd love to have had a dog, but felt it wouldn't be fair to leave her alone all day while I'm at work. How much longer do you need to take Arimidex? Oh and does it bother your fingernails? My fingernails are so soft - and peeling so low, the tips of my fingers look chewed up. I'm not sure if it's caused by the Arimidex or the Herceptin.

Lani thanks so much for your thoughtful and informative response........yes, my interest is in women who are not only Stage 1 but Grade 1 as well. My tumor has already been sent out for pathology twice - to two different labs - once by the radiologist who did the biopsy and the second time by my breast cancer surgeon who's follows a policy of re-testing a tumor before surgery. Both times it showed "well differentiated" which means Grade 1. Then it was tested with FISH twice at two different labs and came up Her2++++. My original onc immediately knew he'd put me on Herceptin - because even though I had the mastectomy - he wanted to be extra-aggressive, like me.

Lani - the size of my tumor was always a bit in question - the radiologist originally said the "nodule" was about 7mm based on what she saw in the mammo and sonogram. No where in the path report of the biopsy did they say what size the tumor was. They said how large the SAMPLES of tissue were. After my mastectomy, the path report said the area was 1.7 cm - but that was including the area of normal tissue that was removed with the tumor during biopsy. Another report said it was .9 cm, with an asterick indicating that it might be smaller - so my onc went with that size. I'm assuming since the size was at least 7mm and no greater than .9 cm that's why the tumor was a Stage 1.

I tried researching Navelbine with Herceptin online, but only found patients who had mets to the liver receiving this treatment. I had switched onc's early on in my treatment to be closer to home, and my new onc agreed that this tx would be OK. Also a friend's sister is the head onc at a major hospital in California - and she emailed me that this tx might be unusual but oncology is part art as well as science and I should be fine. I got the same response from an oncologist online.........STILL I worry that I went through all this chemo (with the infected port that we couldn't use, and painful, burning veins in my arm) and that I'll get a recurrence. I never complained to my original onc about a fear of losing my hair - but he decided that Herceptin works well with ANY chemo - and he said Navelbine wouldn't cause me much hair loss or any heart problems. So while I'm grateful for not having had to suffer those side-effects, my level of anxiety is higher than it probably should be, which is why I'm so grateful for this message board!

[Debbie L.]

Hi all,

I went looking for confirmation of my sense that HER2+ tumors are not any bigger at diagnosis than HER2- ones. It was hard to find much, but I did find (below) a small study that addressed both that, and grade.

I thought that HER2+ grade I would be extremely rare but I found this reference that it's not all THAT rare (10% of HER2+'s, if I read this correctly). Very small study, though.

Also, just from observation, it didn't seem to me that HER2+ tumors were bigger than any others, and this study confirmed that. Again just anecdotally - the women that I talk to with the largest tumors seem more often to be triple negative (and even with those large tumors, they are often node negative - so weird) or ER+.

This study did not look at HER2+ and correlation to lymph node status but my guess is that it would be a positive correlation.

So the next question is what does grade I/HER2+ MEAN? Can someone with this pathology be reassured (seems logical)? Does Herceptin have a role in treating this subtype? (no answers to these questions yet, alas, but we can guess that the answer is "yes", because Herceptin's action is totally different from chemo's, right?)

What about chemo? So far all hints point to chemo's lack of effect on low grade tumors. For awhile, it seemed like it was that chemo was less effective on ER+ tumors but I think that was because they tended to be lower grade.

So it's not simply that low grade tumors are at less risk of recurrence and don't NEED chemo, right? It's that chemo offers little advantage to these cancers, even if (somehow) they had a worse prognosis than the do.

This is mostly speculation on my part. (except the 10% grade I/HER2+ and the lack of correlation between HER2 and tumor size - see copy/paste below). What do you think?

Abstract: The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p < 0.0003), ER (p = 0.0001) and PR (p < 0.0001) negative tumors, over-expression of MIB-1 (p < 0.0005) and high tumor grade (p = 0.0009), while size of the tumor (p = 0.08) and age of the patients (p = 0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification.

[swimangel72]

Thank you for posting this study Debbie - you bring up good questions about the role of chemo in low grade tumors - I guess that's why my first onc didn't recommend chemo to me at all, just the 5 years of Arimidex - until he got my Fish report showing I was Her2+. I'm so happy that Herceptin was available to treat my tumor - as soon as I learned about Her2+ BC, I called my first cousin who is a survivor of 10 years. She didn't know her status - so she called her onc and found out she was Her2- which was a BIG relief to both of us! What a roller-coaster ride this past year has been!

[suzan w]

Lani, my tumor was 8mm, and I think they told me that the stage 2 was because it was Her2+++??
As to the osteoporosis, I had severe osteoporosis before my bc diagnosis. The chemo, arimidex etc was making a bad situation worse, thus the Forteo

[Lani]

her2+ivity does not alter stage.

The TNM staging system has been around for many, many decades as has the grading system.

her2 testing has been around ~ 20-25 years(I just looked up Dr. Slamon's seminal article and it was 22 years old) and has only been done commonly for the last 5-10--3-4 in some areas of the US and 1-2 in some areas of the world. Many countries do not have the means/talent to do the testing at all.

Perhaps what you remember is that despite the small size of your tumor, the fact that it was her2+ caused them to consider you at higher risk than you would otherwise be.

[MJo]

I was Stage I, Grade 2. I think it's interesting that you are Grade I. It does sound confusing -- Grade I tumors supposedly aren't growing as aggressively as Grade 2 or 3 tumors, but Her2 + cancer is aggressive. Maybe you are one for the books! It just confirms that if you have 1000 women with BC, you have 1000 totally unique cancers.

swimangel, I am also grade 1, stage 1, Her2+, and ER+/PR+. My onc was suprised too. We tested three times, all came back positive by FISH but equivocal by IHC (2+). My grade was 1 as I mentioned and KI-67 only 9%, so looked slow growing. My ER and PR were also over 90%. My tumor was 5mm - small like yours. They never found more tumor at mast so I guess was all taken out by biopsy. With small tumor and nodes negative, onc kept saying grade 1, small tumor, no nodes does not look like Her2+, but it sure changed my treatment and prognosis. Instead of 2% chance of spreading, she then said 10-15% ("but I am probably overestimating" she said). So I went ahead and did 6-TCH with herceptin. She also said that they aren't even sure that they are testing for the right thing so I read that as she is not positive that my tumor is Her2+ but I couldn't take the chance since I have three small kids. I finished up chemo about two months ago and just started up tamoxifen. So far so good.

What did your onc say about prognosis? Someone posted this interesting study from CA on breastcancer.org that really shows that not all Her2 is alike. So maybe we are really her2+ but just a different variety.
http://www.asco.org/ASCO/Abstracts+%...stractID=40116

I feel very relieved that I did the chemo even though I am not happy about the chemopause and what an extra ten years of menopause may do to my heart and bones. Onc says tamox will help bones, and then again I may start menstruating again. It is all very confusing.

[Laurel]

I am one of those rare cases, too. I had extensive DCIS which was high grade, and IDS. The invasive component was 7mm, low grade (1), stage 1b, mucinous cancer. Mucinous cancer is rare and considered quite non-aggressive. If I recall correctly only 2% of all breast cancers are mucinous. I had a really low mitotic rate. However, I was ER pos. at 80%, PR pos at 90%, and Her-2 with a FISH of 6.9. and node negative. I was not covered by insurance to have my oncodex score tabulated because with my Her-2 status my onc. said I would be assured to be recommended for chemo.

She recommended 8 rounds of ACTH, 4 AC, 4TH with a year of Herceptin. I am also taking 2 years of Tamoxifen and them will shift to 3 years of an A.I.

I wasn't convinced I needed all that chemo. To be honest sometimes I still wonder, but I knew that I would not have to look back with regret if I should recur. I've fought the good fight.

[Lani]

the MammaPrint people presented a paper regarding their finding that 16% of her2+ breast cancer patients have a good prognosis ie, much closer to the best prognosis group (the ER+PR+her2negatives) than to the rest of the her2+s.

Here is a brief synopsis:

Agendia's Breast Cancer Test MammaPrint(R) Identifies New Subset of Low Risk HER2+ Patients

Recent Study Reveals Substantial Group of Traditionally Miscategorized HER2+ Patients

HUNTINGTON BEACH, California and AMSTERDAM, December 13 /PRNewswire/ -- Dr. Michael Knauer from the Netherlands Cancer Institute today announced data uncovering a substantial group of traditionally miscategorized low risk HER2+ patients. Agendia's highly accurate breast cancer tumor recurrence test, MammaPrint(R), was used to differentiate between patients at high and low risk for recurrence.

HER2+ patients are commonly identified as high risk, yet MammaPrint was able to identify a low risk subgroup of HER2+ patients, who subsequently experienced a 10 year disease-free survival of close to 90 percent even in the absence of (neo)adjuvant trastuzumab (Herceptin(R)) and chemotherapy. Additionally, in a subgroup of highly endocrine responsive HER2/NEU positive patients, MammaPrint(R) low risk patients had no relapse.

The results were presented by Dr. Michael Knauer during the 2008 San Antonio Breast Cancer Symposium (SABCS). In the study population of 169 HER2+ patients MammaPrint(R) classified 16 percent of patients as having a good prognosis signature with a 10-year distant disease-free survival (DDFS) of 89 percent, compared to 84 percent of patients classified as having a poor prognosis signature with a DDFS of 64 percent.

MammaPrint(R)'s robustness is underscored by the 70 gene panel unique to the test and a resulting gene profile that covers all molecular pathways associated with breast cancer. HER2/NEU-overexpression is observed in 15-20 percent of invasive breast cancers and is widely considered to be a negative prognostic factor. As a result, current treatment guidelines classify all HER2-positive breast cancer patients at high risk of relapse, and recommend trastuzumab and chemotherapy.

MammaPrint(R) accurately identified a subgroup of patients with a good clinical outcome in HER2+ early breast cancer. These patients will be further studied in the ongoing MINDACT-trial (Microarray for Node-negative and 1-3 positive node Disease may Avoid ChemoTherapy) to determine the prospects of withholding chemotherapy and/or trastuzumab in HER2+, MammaPrint(R) low risk patients.

About MammaPrint(R)

MammaPrint(R) is the first 'in vitro diagnostic multivariate index assay' (IVDMIA) cleared by the U.S. Food and Drug Administration (FDA). FDA clearance requires clinical and analytical validation and reporting systems to ensure patient safety issues are addressed. Highly accurate, MammaPrint(R) identifies patients with early metastasis--those patients who are likely to develop metastases within five years following surgery. Several authoritative studies have shown that chemotherapy particularly reduces early metastasis risk. In planning treatment, the MammaPrint(R) test result provides a doctor with a clear rationale to assess the benefit of adjuvant chemotherapy in addition to other clinical information and pathology tests.

All MammaPrint(R) tests are conducted in Agendia's CLIA-certified service laboratory. All other breast cancer recurrence assays currently marketed have not been subject to the rigorous FDA clearance process.

[Laurel]

Lani,

That is truly great news. Of course, I cannot help sighing and saying "if only!" If only that test had been around last spring when I needed to make the decision to take adjuvant chemo or not. I suspect at the end of the day, my protocol was overkill, but without the supporting data I chose to err on the side of caution and do the ACTH. Well let's hope it will be made the test du jour for all newly dx'd Her-2 patients!

[suzan w]

Thanks, Lani. This info is indeed encouraging for Her2 early stage cancers! I, too, am too late to benefit from this and chose to go the whole route, chemo/Herceptin. It is great to see that the research continues to make huge advanced in bc treatments. This was a very interesting article!!!

[SoCalGal]

Just want to chime in and say that being er/pr+ is very favorable too and I'm guessing that you are on something long term to address that?

[caya]

Laurel, I just read your post, and it reminded me that my tumour was also mucinous - as well as ER+/ER+ - the first path. report came back as grade 1, and because of the other very favourable "characteristics" - mucinous, and hormone +, as well as a low mitotic score, my onc. just could not believe I was Her2+ ... He sent the tumour out to 2 other labs to verify - the last one, to whom he told me was the guru of path. drs. in Toronto changed it to a grade 2, and verified the Her2+.

I was node negative as well. I hope this new study can help out future women to avoid chemo/Herceptin if it is really proven to be unnecessary. For me, it would have be like 95% sure that I would be okay without the treatment.

all the best
caya

[Laurel]

Caya,

My specimen was sent out to another lab as well because there was disbelief with my surgeon and onc. I suppose that it is rare to have mucinous bc in the first place, and as in our cases, even rarer to have Her-2 + mucinous bc!

I hope this testing becomes the norm. Chemo is a tough go. I would have loved to have avoided it! I would be happy to discontinue the Herceptin, too. I hate this itchy port!

Oh well, what's done is done. No real point in looking back.