Polite Explanations are Welcome....

AlaskaAngel

Can someone explain what the rationale is that is being used to hold up progress?

TEN years ago when I was diagnosed, it was possible to do comparison studies in other countries that showed the effectiveness of such treatment as ovarian ablation plus "X" drug, versus standard chemotherapy for early stage bc:


http://jncimonographs.oxfordjournals.org/content/2001/30/67.full

and


http://jncimonographs.oxfordjournals.org/content/2001/30/67/T2.expansion.html

How long will it take for us to get a comparison of either ovarian ablation and trastuzumab alone (or possibly trastuzumab plus lapatinib) for premenopausal early stage HER2 positive bc patients, versus standard chemotherapy, in this country?

-AlaskaAngel

sweetbean

AA,

You'd have to find willing participants first.   Ovarian oblation looks like a possible option for patients who have a less aggressive cancer, which is pretty much the opposite of Her2+ cancers.   Most people want the most effective treatment. 

AlaskaAngel

sweetbean,

I wondered about that too, but they were comparing node positives, which may be as = to HER2 positives that are early stage.

There always will be the perception that doing the most painful, difficult, toxic treatments = doing the most effective treatments. However, the main difference IMO would be just how much effect actually occurs through the destruction of the cancer cells, and not in the hormonal manipulation. I understand that chemo probably does not help in dealing with stem cells, also.  My understanding is that chemotherapy per se is less effective for those who are HR+ and more effective for HR-.

So it may be that it actually is the most effective treatment, in that it preserves the immune system whereas chemo is very hard on that.

A.A.

sweetbean

I don't know.  That recent study that showed that over 50% of Her2+ patients had a CPR on Taxol, Herceptin, and Tykerb was pretty convincing.  If I had a choice between that and OA, I'd go with the treatment that gave me the best chance for a CPR.  

AlaskaAngel

That is what I think might be influencing success vs failure. Those with the highest rate of PCR on the regimen (which included Taxol) were ER-. Those who were ER+ didn't do as well and might actually do better with ablation plus H and L instead of chemo.

I also think maybe it would be important to tease out the effects of the support drugs somehow, like the effects based on who got what steroid dose, etc.

A.A.

AlaskaAngel

Sometimes in looking back at discussions that have gotten very passionate, one thing I've noticed is that each person's individual cancer characteristics often influence their position without anyone realizing it. HER2 positives who are ER negative naturally tend to be more adamant about the importance of chemo, and those who are ER positive tend to be more adamant about hormonal therapy advantages.

sweetbean

I am triple postive - I think I was 90%ER and 70%PR.  I had a great response to chemo and it would have been better if I had gotten Herceptin at the right time.  I am also very committed to taking my Tamoxifen.  the doctors felt that it was because I was Her2+ that I had such a good response.

I think the idea of offering Her2+ people OA instead of chemo is just kind of dangerous.   

Enjoyful

My latest cancer was 100% ER+ and it responded beautifully to chemo.  After the second treatment, the cancerous lymph nodes had shrunk significantly.  Two years later, I'm still disease-free, thanks to chemo and Arimidex.

I truly do hate Arimidex because of the side effects, but if it keeps the beast at bay I'm all for it.

AlaskaAngel

sweetbean, Scootaloo, and hillck,

Once we have chosen and completed a particular course of therapy for our individual situation, we are each hoping that what we did worked and will continue to work. I did CAFx6, which is sometimes still recommended, although AC + TH or TCH more often seems to be recommended for HER2 positives. I was ER+, PR+ and HER2+++.

But...

hillck and sweetbean were ER+, PR+, and HER2 positive too.... and did not have CAFx6 (because they were treated more recently). And I think they were recommended to have trastuzumab, which I was recommended not to have.

Each of us hopes that whatever they did, worked -- even though our tumors had the same ER, PR and HER2 characteristics, and even though our treatments each differed significantly. None of us can prove that any of our different treatments definitely worked because none of us have any definite proof that our cancers would ever come back. We have statistical estimates, but no scientific certainty that any of us ever needed the treatment in the first place.

That doesn't mean doing treatment was not appropriate.

In that same way, we have no studies to prove that any of us (or perhaps that someone else who might also be ER+, PR+ and HER2 positive) would have any less chance of staying without recurrence by doing surgical ovarian ablation plus trastuzumab, or even by doing surgical ovarian ablation plus trastuzumab and lapatinib. We can "believe" that chemotherapy of one sort or another is better and "believe" that even with all the side effects from it, it is a much higher standard, but no one has proven scientifically that it actually is better.

The information that I posted showed that, based on information from 2001 (before trastuzumab), ovarian ablation was equal to chemotherapy for treatment of bc patients at high risk for metastasis (those with positive nodes).

A.A.

AlaskaAngel

Trastuzumab May Benefit Patients with Very Small & Low-Grade Breast Tumors Laino, CharleneOncology Times .      31(4) Clinical Spotlight Supplement:2-4, 25 February 2009.        doi: 10.1097/01.COT.0000346950.83846.bdAuthor InformationSABCS Abstracts 701 and 702Adjuvant systemic therapy with the anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab (Herceptin) should strongly be considered in early-stage breast-cancer patients with very small and low-grade HER2-positive tumors, researchers reported at the San Antonio Breast Cancer Symposium.A US team came to that conclusion after finding that HER2 positivity is a powerful negative prognostic factor for patients with node-negative disease and tumors that are 1 cm or smaller. In addition, UK researchers found that HER2 positivity is associated with an increased risk of death due to breast cancer in patients with node-negative, histological Grade 1 or Grade 2 disease.Together, the studies show that patients who are traditionally defined as low risk, but who are HER2-positive, have a poor prognosis. This is important because it tells us that HER2 status has a prognostic role even in low-risk tumors, said Angelo Di Leo, MD, PhD, Head of the Sandro Pitigliani Medical Oncology Unit and Chair of the Department of Oncology at the Hospital of Prato, Tuscany Cancer Institute, in Italy. Dr. Di Leo moderated the well-received, early-morning oral poster discussion of both studies.Physicians need to consider offering these women Herceptin-based therapy in the adjuvant setting, said the senior investigator of the US team, Ana M. Gonzalez-Angulo, MD, MSc, Assistant Professor of Medicine in the Departments of Breast Medical Oncology and Systems Biology at the University of Texas M. D. Anderson Cancer Center.The number of patients diagnosed with HER2-positive tumors 1 cm and smaller continues to increase as breast cancer surveillance and early-detection methods become increasingly sophisticated, she said.* * * *Current Guidelines Current treatment guidelines do not recommend that trastuzumab be given to women with HER2-positive tumors smaller than 0.5 cm and suggest only that clinicians discuss trastuzumab treatment with women whose tumors are 0.5 to 1 cm in size. The reason, Dr. Gonzalez-Angulo explained, is because these women were largely excluded from the definitive trials confirming the benefit of the drug.Five randomized, Phase III clinical trials reported significant improvement in disease-free and overall survival with trastuzumab administered in conjunction with adjuvant chemotherapy for early-stage HER2-positive breast cancer. However these studies included principally node-positive cases, and four trials excluded patients with tumors 1 cm or smaller that were node-negative.* * * * As a result, available data on the risk of recurrence in women with very small, node-negative tumors are limited, she said.To help fill in the knowledge gap, Dr. Gonzalez-Angulo, Ronjay Rakkhit, MD, Chief Fellow in the Department of Oncology at M. D. Anderson and the study's first author, and colleagues used the center's Breast Cancer Research Database to evaluate the risk of recurrence in women with Stages TIa and TIb, node-negative, HER2-positive breast cancer.A total of 965 patients with node-negative invasive breast tumors 1 cm or smaller were included in the analysis. Patients whose receptor status could not be analyzed and/or had received adjuvant chemotherapy or trastuzumab were excluded.Ten percent of the patients had HER2-positive tumors, defined as gene amplification on fluorescence in situ hybridization (FISH) and/or overexpression of three or more receptors, with strong membranous staining in at least 10% of cells, on immunochemistry.In addition, 77% of patients were hormone-receptor positive, and 13% were triple receptor-negative-that is, estrogen receptor-negative, progesterone receptor-negative, and HER2-negative. Women with triple receptor-negative disease face a particularly poor prognosis.The median age of the patients at diagnosis was 57. Two thirds had Stage TIa disease, and the rest had Stage TIb.To validate the findings, a second cohort of 350 cases with the same inclusion criteria and similar follow-up time were obtained from collaborators at the General Hospital Leoben in Austria and Institute Jules Bordet in Brussels.* * * *US Study Results Results of the M. D. Anderson dataset showed that the five-year, recurrence-free survival rate in women with HER2-positive tumors was 77% vs 94% in women with HER2-negative tumors.In multivariate analysis, this translated into a significant 2.68 times higher risk of recurrence in patients with small HER2-positive tumors, compared with patients with small HER2-negative tumors, Dr. Gonzalez-Angulo reported.* * * * The five-year distant recurrence-free survival rate was 86% in women with HER2-positive tumors, compared with 97% in women with HER2-negative tumors. This corresponded to a 5.3 times higher risk of distant recurrence in patients with HER2-positive tumors in the multivariate analysis.In addition, women with HER2-positive tumors had 5.1 times the risk of recurrence and 7.8 times the risk of distant recurrence, compared with women with hormone receptor-positive tumors.There was no significant difference in the risk of recurrence or distant recurrence in patients with Stage TIb vs Stage TIa disease.As expected, women with triple-negative tumors were at particularly high risk of recurrence, Dr. Gonzalez-Angulo added. These women had a five-year recurrence-free survival rate of 85%, and a five-year distant recurrence-free survival rate of 96%.The European subset confirmed the M. D. Anderson findings and showed reproducibility, she said. The five-year, recurrence-free survival rate in women with HER2-positive disease was 87%, compared with 97% in women with HER2-negative tumors, a significant difference.Funding for the study was provided by the American Society of Clinical Oncology, the National Cancer Institute, and the Nellie B. Connally Breast Cancer Research Fund.* * * * UK Study For the UK study, University of Glasgow researchers sought to determine the number of patients both who were eligible for and who actually received trastuzumab therapy for early-stage breast-cancer at their institution in 2006. They also performed a retrospective analysis of the impact of HER2 status on survival of low-grade, node-negative HER2-positive patients who would currently be deemed ineligible for trastuzumab treatment.For the first part of the study, data for all 951 patients diagnosed with early-stage breast cancer in 2006 were recorded prospectively in a database.A total of 110 of the women had HER2-positive tumors, 57 (52%) of whom received trastuzumab therapy. Of the 53 (48%) patients who did not receive trastuzumab, 25 (43%) were considered to be at low risk of recurrence due to small, node-negative, low-grade tumors, reported Sian M. Tovey, MD, a Clinical Lecturer in the Section of Surgical and Translational Research at Glasgow Royal Infirmary.Then, the researchers retrospectively analyzed a cohort of 367 women diagnosed with Grade 1 or 2, node-negative disease between 1980 and 2002. A total of 89% of cases were estrogen-receptor positive, and 72% had tumors smaller than 20 mm. Ten percent received chemotherapy, and 91% received endocrine therapy.The five-year breast cancer-specific survival rate was 96% in the 348 women with HER2-negative disease, compared with 68% in the 19 women with HER2-positive disease. This translated to a significant 6.8 times higher risk of dying of breast cancer for women with low-grade, HER2-positive vs HER2-negative disease, Dr. Tovey reported.This reduction in survival in HER2-positive cases persisted when patients were split into subgroups by estrogen-receptor status, tumor size-20 mm or greater versus less than 20 mm-and age-under 50, 50 to 65, and over 65 years, she said.What this means is that no HER2-positive patient should be considered low risk. It's the biology of the tumor, not the grade or size, that matters. HER2-positive tumors are known to be aggressive, with poor differentiation and a high proliferation rate.They should all be considered for Herceptin therapy, she continued, adding that the findings are already changing practice at her institution.* * * *Uniform Praise The research was uniformly praised by clinicians and researchers, many of whom crowded around the posters prior to the discussion session.Dr. Di Leo noted that in the Herceptin in Adjuvant Breast Cancer (HERA) and National Surgical Adjuvant Breast and Bowel Project B-31 (NSABP B-31) trials, the benefit of trastuzumab seemed to be independent of disease stage. One could therefore speculate that trastuzumab would help patients with very small and/or low-grade tumors who are currently not being routinely treated, he said.Minetta C. Liu, MD, Assistant Professor of Medicine in the Division of Hematology/Oncology at Lombardi Comprehensive Cancer Center, said that one of the biggest debates in the field of breast cancer is whether to treat very small tumors.Since they had such small tumors and presumably a better prognosis, these women weren't included in [the pivotal clinical] trials of trastuzumab. But these new data show that without trastuzumab therapy, these patients clearly have a worse prognosis, she said.Dr. Liu noted said that some clinicians are already offering trastuzumab to patients with smaller tumors. The new data may make more physicians think about using it, she said.Charles L. Vogel, MD, Senior Research Advisor in Breast Cancer at Aptium Oncology in Boca Raton, FL, said, These two studies are tremendously important. Whenever you go to a meeting, everyone always asks what to do with very small tumors.Before we had no answers, but now we have a few nice pieces of data to support trastuzumab therapy, he said.Dr. Vogel added that while he believes many physicians treat Stage TIb tumors, they draw a line in the sand at 5 mm.The M. D. Anderson study, which showed no significant difference in recurrence rates between women with Stage TIa and TIb HER2-positive tumors, suggests that even the smallest tumors may benefit from trastuzumab, Dr. Rakkhit said.Dr. Gonzalez-Angulo said that one open question is whether these patients will benefit from trastuzumab alone or whether they need trastuzumab plus chemotherapy.

voraciousreader

According to the authors of the study, Medscape Medical Reporter Roxanne Nelson writes:

Ideally, prospective randomized trials of trastuzumab-based treatment are needed for this population, but they are not likely to ever be conducted for a number of reasons, the authors write. Because of the low incidence of small HER2-positive breast cancers and the relatively low event rate, a large number of patients would be needed, which would be expensive. The design of trials has already proven difficult to agree upon, and successful recruitment to a randomized trial with a no-treatment group would be challenging. Finally, the choice of treatment for the investigational group is controversial.

Taking this into consideration, they suggest that the "next best approach would be a nonrandomized prospective study." Additional supportive evidence could be garnered from ongoing trials that include patients with small HER2-positive tumors.

The authors offer 2 more recommendations. One is to create prospective databases on the management of patients with HER2-positive cancers, which would provide retrospective analyses of outcomes associated with different treatments. The second is to incorporate molecular markers and multigene assays into clinical datasets, which might help identify and stratify relative risk within this subgroup.

"As in other areas of breast cancer management, this type of approach will eventually lead to a much more accurate prediction of which systemic therapies, if any, will most benefit each individual patient with these difficult, small, HER2-positive cancers," they conclude.

voraciousreader

And, in light of the Lancet announcement last week, IMHO the guidelines for HER2+ tumors will probably be updated to include the use of more Herceptin AND chemotherapy.  The news last week is nothing short of spectacular for women with HER2+ tumors:

MedPage Today) -- Significantly more women with HER2-positive breast cancer achieved complete tumor resolution when they received two targeted agents before surgery instead of one, results of a large European study showed.

Neoadjuvant therapy with trastuzumab (Herceptin) and lapatinib (Tykerb), in addition to chemotherapy, led to pathologic complete response (pCR) in more than half of patients, Jose Baselga, MD, of Massachusetts General Hospital in Boston, and co-authors reported online in The Lancet.

That compared with the 25% to 30% of patients who achieved complete response on trastuzumab or lapatinib alone.

Although the study did not evaluate the effect of treatment on survival, prior studies have shown that pCR correlates with improved disease outcomes in patients treated with trastuzumab and chemotherapy.

"This open-label, multicenter, phase III study showed that dual inhibition of HER2 with lapatinib and trastuzumab in combination with paclitaxel is better than single-agent HER2 targeting," the researchers wrote in conclusion.

"Our study also supports investigation of novel targeted agents for breast cancer in the neoadjuvant setting, when tumors have not yet acquired resistance to therapy and when chances of clinical benefit are highest."

The published results updated and affirmed findings from an initial report more than a year ago.

Results of another study, published simultaneously in The Lancet Oncology, showed that neoadjuvant therapy with trastuzumab plus chemotherapy resulted in a significantly higher rate of pathologic complete response compared with lapatinib and chemotherapy.

Both targeted agents inhibit HER2 but have different mechanisms of action, providing a rationale for evaluating them in combination. Preclinical and clinical evidence had suggested that combining lapatinib and trastuzumab would result in more potent inhibition of HER2 compared with either drug alone.

Baselga and colleagues reported final results from a trial called NeoALTTO, which compared lapatinib, trastuzumab, and the combination for women with HER2-positive breast cancer.

All patients started treatment with the assigned targeted therapy. Paclitaxel was added after six weeks, and neoadjuvant therapy continued for a total of 18 weeks. Surgery followed completion of neoadjuvant therapy, and patients received adjuvant treatment with paclitaxel and the same anti-HER2 regimen as in the neoadjuvant.

The final analysis involved 455 with HER2-positive primary breast cancer larger than 2 cm in diameter. The primary endpoint was pCR, as defined by National Surgical Adjuvant Breast and Bowel Project criteria.

The targeted combination plus paclitaxel resulted in a pCR rate of 51.3% compared with 29.5% in patients who received trastuzumab plus paclitaxel and 24.7% for the lapatinib-paclitaxel arm (P=0.0001). The pCR rate did not differ between the trastuzumab and lapatinib arms.

No major cardiac dysfunction occurred during the trial. Patients treated with lapatinib had higher rates of grade 3 diarrhea (23.4%, 21.1%, respectively) and grade 3 liver-enzyme alterations (17.5%, 9.9%) compared with trastuzumab (2%, 7.4%). Otherwise, adverse events were similar among treatment groups.

Authors of a related commentary said that trials of targeted therapies could change the clinical evaluation process.

Rigorous investigation of a biologic agent in the neoadjuvant setting might obviate the need to begin evaluation of a drug in advanced disease before moving to the neoadjuvant and adjuvant settings, wrote Michael Gnant, MD, and Guenther G. Steger, MD, of the Medical University of Vienna in Austria.

Such an approach to clinical investigation could substantially reduce development costs and bring promising new drugs to patients more quickly, they wrote.

However, they also pointed to NeoALTTO as an illustration of unresolved issues in clinical use of targeted agents. Optimal treatment duration, selection and use of biomarkers, and the expense of combining two costly drugs must be rigorously examined, wrote Gnant and Steger.

The article in The Lancet Oncology provided details of another European trial, called GeparQuinto, a phase III randomized study involving 620 women with previously untreated operable or locally advanced HER2-positive breast cancer.

Patients with clinical stages T1 through T4 were eligible, depending on nodal and hormone-receptor status. All patients received neoadjuvant chemotherapy with the combination of epirubicin, cyclophosphamide, and docetaxel. They were randomized to neoadjuvant trastuzumab or lapatinib.

The primary endpoint was pCR. When the trial ended, 30.3% of patients in the trastuzumab arm and 22.7% of those in the lapatinib arm had achieved pCR, which translated into an odds ratio of 0.68 in favor of trastuzumab (P=0.04).

The trastuzumab regimen was associated with higher rates of edema (39.1% versus 28.7%) and dyspnea (29.6% versus 21.4%) and the lapatinib regimen with more diarrhea (75.0% versus 47.4%) and skin rash (54.9% versus 31.9%).

Premature discontinuation rates were 14.0% with trastuzumab and 33.1% with lapatinib.

"This direct comparison of trastuzumab and lapatinib showed that pathologic complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab," Gunter Von Minckwitz, MD, of German Breast Cancer Group in Neu-Isenburg, and co-authors wrote in conclusion.

"Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as a single anti-HER2 treatment in combination with neoadjuvant chemotherapy," they wrote.

The results confirm those from a previous report at the San Antonio Breast Cancer Symposium.

Three important lessons can be learned from the results of GeparQuinto, Stephen K. Chia, MD, of the British Columbia Cancer Agency in Vancouver, B.C., wrote in an accompanying commentary.

1. Lapatinib plus chemotherapy offers no advantages over chemotherapy plus trastuzumab in the adjuvant setting, a conclusion drawn recently by investigators in a large randomized trial that compared the two agents as adjuvant therapy for patients with early-stage HER2-positive breast cancer.
2. The preoperative (neoadjuvant) setting is ideally suited for testing new therapies.
3. Clinical researchers and patients have embraced the preoperative model as standard of care and as a strategy for evaluating new therapies.

The NeoALTTO trial was supported by GlaxoSmithKline.

Baselga disclosed a relationship with Roche. Coauthors disclosed relationships with GlaxoSmithKline, Roche, Novartis, Amgen, Abbott, AstraZeneca, Pizer, and Bristol-Myers Squibb. Coauthors included employees of GlaxoSmithKline.

Gnant disclosed relationships with AstraZeneca, Novartis, Roche, Schering, Pfizer, Novartis, AstraZeneca, Sanofi-Aventis, GlaxoSmithKline, and Amgen. Steger disclosed relationships with AstraZeneca, Roche, Amgen, Novartis, and GlaxoSmithKline.

Primary source: The Lancet Source reference: Baselga J, et al "Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): A randomized, open-label, multicenter, phase III trial" Lancet 2012; DOI:10.1016/S0140-6736(12)61846-3.Additional source: The Lancet Source reference: Gnant M, Steger GG "Dual inhibition of HER2 in breast cancer treatment" Lancet 2012; DOI:10.1016/S0140-6736(12)60068-3.Additional source: Untch M et al. "Lapatinib versus trastuzumab in combinatioin with neoadjuvant anthracyclline-taxane-based chemotherapy (GeparQuinto, GBG 44): A randomized phase III trial." Lancet Oncol. 2012;doi:10.1016/S1470-2045(11)70397-7. Source reference: Untch M et al. "Lapatinib versus trastuzumab in combinatioin with neoadjuvant anthracyclline-taxane-based chemotherapy (GeparQuinto, GBG 44): A randomized phase III trial." Lancet Oncol. 2012;doi:10.1016/S1470-2045(11)70397-7

AlaskaAngel

There are some significant problems they fail to mention in their discussion.

"Because of the low incidence of small HER2-positive breast cancers and the relatively low event rate, a large number of patients would be needed, which would be expensive."

So their answer is: Let's keep the status quo in recommending that in behalf of this group with a "low incidence" of small tumors and a "relatively low event rate", a much larger group should take on the very expensive treatment with chemotherapy, and for the majority, an unnecessary treatment that has multiple known side effects that also cost more money along with all the support drugs that also cost more money, and does not work in some patients even though they complete treatment, and eventually fails in some patients who do the treatment.

"Finally, the choice of treatment for the investigational group is controversial."

And they don't consider using such expensive treatment with such uncertain results for so many that never need it at all to be as controversial, if not more so.

"The news last week is nothing short of spectacular for women with HER2+ tumors:

MedPage Today) -- Significantly more women with HER2-positive breast cancer achieved complete tumor resolution when they received two targeted agents before surgery instead of one, results of a large European study showed.

Neoadjuvant therapy with trastuzumab (Herceptin) and lapatinib (Tykerb), in addition to chemotherapy, led to pathologic complete response (pCR) in more than half of patients, Jose Baselga, MD, of Massachusetts General Hospital in Boston, and co-authors reported online in The Lancet.

That compared with the 25% to 30% of patients who achieved complete response on trastuzumab or lapatinib alone."

The value of the addition of chemotherapy for early stage bc is not demonstrated. The value of using the two drugs (trastuzumab and lapatinib) rather than only trastuzumab OR lapatinib, is demonstrated. That is good news. It increases the likelihood that using trastuzumab and lapatinib without chemotherapy would be helpful for HER2 positive patients.

A.A.

voraciousreader

Yes. A trial would be expensive.... However, once again the researchers eloquently explain additional reasons that would prohibit the study. Once again you choose to parse words without appreciating the full context.

sweetbean

 I don't know about that, AA.  I had good response just on chemo for my (then unknown) Her2+ tumor.  so there is definitely benefit.  I just wish I had gotten Herceptin and Tykerb as well.

AlaskaAngel

Good information, sweetbean, thank you. Chemotherapy does produce some ovarian ablation, which reduces the hormonal influence for HR positives. (So would ovarian ablation by other means.)

AlaskaAngel

The reason one shouldn't take the assumptions reached for most studies advocating the use of chemotherapy for HR positives as being absolutely true is that unfortunately the same mistake continues to be made over and over about our hormonal basis for cancer. Those studies include the effects of chemotherapy (including ovarian ablation).

When one includes ovarian ablation by other means for the HR+ patient, plus specific treatment for the patient's case (such as trastuzumab) but that does not include chemotherapy, then one is using more comparable therapies.

That argument always generates the question, "But what about those who are already menopausal?"  Unfortunately, the tendency has been to assume that means one's ovaries don't produce any further hormones after one's periods stop. But there is some evidence to the contrary, indicating that even though periods stop, the ovaries continue to produce some hormones. So, it would be helpful to have either better indicators of absolute ovarian ablation through menopause, or else substitute surgical ovarian ablation to be certain.

That is why IMO, chemotherapy plus trastuzumab has more disadvantages than advantages over surgical ovarian ablation plus trastuzumab.

AlaskaAngel

AlaskaAngel

Your question at the end is a good one, Hillck, and I have seen something indicating that AI's might not address all sources of estrogen, but I don't have anything to cite for that so I can't say.

The problem is that we stay more or less blind to the awareness that many patients who undergo chemotherapy do resume having periods, so chemotherapy doesn't always have a lasting effect in terms of ovarian ablation, whereas surgical ablation does. We can't even tell if chemotherapy given at later ages produces complete ovarian ablation, since periods don't always resume but there can still be ovarian hormonal production after chemotherapy -- whereas with surgical ablation, hormonal production from the ovaries stops.

This is another reason why it is actually possible that for HR+ patients, surgical ovarian ablation may have better results than chemotherapy. It is easy to assume that using really nasty stuff is better, but for HR+ patients it may not be.

The counter argument to that, of course, is that chemotherapy is intended also to kill actual cancer cells, whereas surgical ovarian ablation would not (although it might result in reduction of a tumor due to lack of as much hormonal support for the tumor). The question is, is the added effect of surgical ovarian ablation equal to (or better than) that of the cell kill by chemotherapy? As I understand it, chemotherapy likely does not kill stem cells.

A.A.

sweetbean

Wait, AA, are you saying that I had a good response to chemo because it acted like ovarian ablation?  I had significant shrinkage during my first two rounds of AC, when I was still getting my periods.   Estrogen also does good things for your body, too (how about sex for starters) - the important thing is to get your body to process the estradiol down non-carcinogenic pathways.  

OA sounds hard on your body.  Chemopause wasn't that much fun - why would I choose something permanent over something temporary? 

Also, if OA was the answer, then you'd see a lot fewer post-meno women in progression and that isn't the case.   

angelsister

Sorry to butt in but oncos explain that bc responds well to treatment compared to other cancers because there are lots of different therapies to choose from and change over to when/if there is a progression or one stops beong effective. This is the reason that my sister freaked out the doc who fonally confirmed that she had ILC and that her bone cancer was secondary to that...and she responded by saying well thats good news! surely the reason for good outcomes for bc patients is that there are cytoxic chemos, hormone therapies - surgical or chemical and rads and herceptin for certain tumours. Reducing the hormone impact on the cancer cells is really important but its just one of the weapons but your right...we dont know which of those sodding cancer cells will respond to which treaments thays why oncs play safe when the stats support that approach. If a cancer is aggressive and likely to recur...why wouldnt i go with the most robust option? Cant think of a reason? As ststed previously, even removing the ovaries or being well into menopause doesnt mean estrogen doesnt still stimulate cancer growth. I wish taking your ovaries out was a simple answer to this disease but it just isnt. My sister had her ovaries out 20 years before she was diagnosed with stage iv. She was defo in menopause, had long since stopped hrt to preserve her skeleton, skin etc. She was stil prescribed ai's as her cancer was er+. Estrogen isnt just produced by the ovaries and chemo's main aim isnt blocking estrogen, thats why its combined with other treatments. Kinda like taking one drug to kill cells and another to stop the little buggers growing back!!?!????

AlaskaAngel

sweetbean and cynsister, you are both really hitting the same question.

I'm not saying that you or anyone shouldn't have the right to the therapy of your choice among the various options. What I am saying, is that as long as research has failed to to do the homework to prove that chemotherapy plus trastuzumab is better for HR+ HER2 positives than surgical ovarian ablation plus trastuzumab, and since we already know that surgical ovarian ablation was equal to CMF or CAF, why shouldn't patients be able to choose to have surgical OA plus trastuzumab if they do not want chemotherapy?

If you have a strong belief in chemotherapy plus trastuzumab over surgical ovarian ablation and trastuzumab and they are equal, wouldn't you want the right to choose?

Surgical ovarian ablation has other disadvantages, just like chemotherapy does.

A.A.

P.S. Sweetbean, I see a lot more postmeno women who have done chemo who have progression. I'm not saying that surgical OA has been proven to be better than chemo. I'm saying that as long as OA has been proven to be equal to CAF or CMF, and other studies still need to be done, why not provide openly provide that choice so that women know it is there? You are forgetting those women who end up without either therapy because they don't want or can't afford all the ecomonics involved with chemotherapy, being off work, having to pay for child sitters, losing income, etc. etc. I think we need to acknowledge that there are women who turn it down for lots of reasons, when they would have been able to do surgical OA.  Of course it isn't fantastic to deal with sexual issues, but I didn't do surgical OA so from what you are saying I shouldn't have the same problem -- but I do..... (I am 10 years out from chemo and you are not).

angelsister

Absolutely! I think everyone has the right to choose too.

Do you think thst the research that you point to which is 10 years old had been superceded by better chemos and herceptin etc and thats why they dont redo comparative studies? They have the data and survial rates for oa, chemo, chemo and oa etc and if new combos do better in terms of percentages? Then why go backwards?

sweetbean

When you say surgical OA, you mean the removal of the ovaries, correct?  Just clarifying....

For me, it is because that treatment just doesn't sound effective for Her2+ tumors.  Running a study would mean putting women through a permanent procedure that might not work.  It's not like the recent study on Herceptin vs. Tykerb that showed that Tykerb wasn't effective alone, so everyone immediately got switched to Herceptin.  If the study you are proposing doesn't work out, it's, "Well, THAT didn't work.  Sorry about your ovaries.  I guess you'll have 15 years of extra menopause.  My bad."  

Also, if you have a treatment (Taxol + Herceptin + Tykerb) that causes CPR in more than half the patients, why would you do anything else?  It would just seem incredibly irresponsible to deny women their best chance at a CPR. 

sweetbean

And honestly, I bet if you looked long and hard enough, you could find an onc willing to just give you Herceptin and a surgeon willing to yank out your ovaries.  But to ask them to put their stamp of approval on it as an equally effective treatment?  I'm sorry, I just can't see it happening.

angelsister

Do you have a lot of difficulties ten yesrs after chemo AA? Sorry about the typos im using my phone

AlaskaAngel

sweetbean and cynsister,

Yes -- TCH or AC+TH have shown more success (although there is confusion there too because some get different drugs for the "C" part). But as long as the researchers and the physicians aren't the ones having to "do the time" themselves and they have trouble getting a round tuit when it comes to other therapy trials, then I don't understand your point. I see quite a few patients getting CAF or CMF for treatment. Why are their oncs allowed to use it for them, if it is so clearly absolutely essential that everyone get the the "best" chemo? As long as there is the freedom for them to openly substitute CAF or CMF, then why can't they openly substitute surgical ovarian ablation for those who WANT it instead?

A.A.

AlaskaAngel

cynsister,

As others like to remind me, I don't have recurrence (whether it is because I  never needed treatment at all, or because of what natural solutions I have added, no one can say).

But yes, I have had more problems over time since treatment. I think it is also an indicator for those now in treatment as to what they will face "later on". As I mentioned elsewhere, I was told at my major cancer center in Seattle that patients who are more than 2 years out from treatment will be refused psychological or psychiatric counseling there for any problems related to their cancer. An effective way to indicate there "are no such patients".

A.A.

angelsister

Can you access counselling any where else? I guess ten years out they'd consider you an advert for the treatment you had. Do you have reason to think you'd have done better with a different plan like oa? I know these are personal questions so feel free to tell me to mind my own!

AlaskaAngel

Thanks, cynsister. But do we want to just try to find someplace else to go that doesn't have to be accountable for the treatment that caused the problems, and have others get the same result?

We each have preferences about what works and what doesn't. But what still shocks me today is knowing that when I specifically asked a highly respected professional oncologist about doing surgical OA instead of CAFx6 back in 2002, which was my preference, he failed to tell me they were considered equal..... and even more shocking, ten years later everyone here still apparently believes that no chemo is equal to surgical OA because oncs like mine still are not honest about it.

To some of us, a nontoxic treatment IS better. There is a tendency in our society especially to "take the bad medicine" instead because taking medicine and getting it over with and then "getting back to normal" is what modern society believes in.  What people don't accept so well is that only those who are younger at time of treatment are likely to get back to something close to normal, and the aging from it brings about faster changes for them, and those who do get back to normal are more likely to recur.

digger

AA,

Without disrespecting you, I would ponder whether or not it's time to move on.  I didn't want a mastectomy, barely a moment goes by without my missing my breast or wondering if I did the right thing.  And it's three years later.  But at the same time, if I gave too much time to wondering the what-if's and why's, I would never be able to get on with my life, you know?  I made the best decision with the information I had at the time, and it's done, and there's no turning back, so that's it and while I still physically hurt every day from the surgery, I don't let it take over my life. I won't let it.

So while what happened to you was terrible, and it's okay to grieve, a part might want to move on as well.  Just a thought.  Too much agonizing can really take you over after awhile.

orange1

AA - you seem to advocate ovarian ablation as an alternative to chemo quite a bit - but you fail to mention the side effects of ovarian ablation - loss of libido, joint pain, wrinkles, osteoporosis, increased cardiovascular risk, stomach flab, loss of muscle mass.  This must be endured for years (until you reach menopause, or beyond (in some of your posts, you advocate ovarian ablation even for post-menopausal women)).  So you are advocating treatment with many long term side effects.

Personally, if I could have my hormones back - I would endure the TEMPORARY side effects of the TCH chemo I had multiple times (temporary - except for the damned chemopause).  Chemo stunk in the short term, but I find long term chemopause (essentially ovarian ablation) much more distressing.