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Herceptin or Trastuzumab: Efficacy, Side Effects

an IV Drip

 

Herceptin, generic trastuzumab, is a new treatment for breast cancer made by Genentech.  It is a humanized antibody to the HER2 receptor, which is over expressed in 20-30% of breast cancer.  By binding to that receptor and damaging malignant cells, Herceptin can help treat breast cancer.

Herceptin is a powerful, targeted treatment for breast cancer.  Unlike chemotherapy, it doesn’t attack all cells.  That said, it is somewhat expensive, up to $100,000 per year, and it can cause serious cardiac issues.

It is a breakthrough, yet still being heavily investigated to figure out its ideal uses.

What is it?

Herceptin is a pretty funky treatment.  It’s a lot like a heat seeking missile that, ideally, targets cancerous breast cells, ignoring healthy ones.

To make Herceptin, researchers played with the immune systems of mice to generate antibodies – a type of defensive molecule – that would target a specific type epidermal growth factor receptor.  They then fused the part of the antibody that gave targeting ability to a human antibody.

The final product is 95% human, 5% mouse.  This is very important because if a treatment looks too “weird” to the immune system, it will attack it like a foreign invader.

Herceptin binds to cells that express HER2 and inactivates them by various methods.  This is important because HER2 is a type of growth receptor that, if you have too much of it, makes your cells grow too rapidly.  HER positive breast cancers are typically more aggressive than those that aren’t.

Herceptin may also interfere with vascular endothelial growth factor, something which promotes blood vessel growth near tumors.  This is important because cancer needs a steady flow of blood to grow.

How well does Herceptin work?

Studies have looked at many different uses for this medication and they seem mostly positive.  One study showed that adding Herceptin to chemotherapy over two years had a 12% better disease free state and an absolute reduction in risk of death by 2.5%.

That’s in combination with other treatments, which is the typical use.  But it also can work by itself, showing that it’s a potent treatment in its own right.  As sole treatment for HER2+ metastatic breast cancer, one study looked at 104 women who were unable to take typical chemotherapy whether for personal or medical reasons.  26% of the women had an objective response with 7 complete remissions and 23 partial responses.  And an additional 13 women had some response or delayed disease progression.

Another analysis of Herceptin’s use in certain types of advanced breast cancer cases showed an increase in survival from 20.3 to 25.1 months.  Additionally, Herceptin may be effective in preventing cancer recurrence.  Of course, as a preventative measure, it is on the pricey edge.

What are issues?

Herceptin works only in HER+ cancers, as it targets that receptor.  Of those cancers, it may work best in those that are specifically 3+ not 2+, which further reduces the situations it can be best used.

We are also not 100% clear as what situations call for Herceptin.  There are many different stages in breast cancer, ranging from slight abnormal growths to full blown metastatic cancer.  Additionally, there are situations when the breast cancer has been removed, or doesn’t fully respond to treatment, with many permutations.

As of writing, the exact dose of Herceptin to be given as well as over what time period at what intervals has not been fully determined.  This is important because we want to use the minimal amount that is effective.

Also Herceptin is delivered by an IV infusion which may be an issue with long term use.  Both for inconvenience and for the possibility of collapsed veins and/or other events associated with long term IV use.

We are also still unclear on the exact chemotherapy combination that works best with it.  It appears to have a synergistic effect with docetaxel, additive with others, and possibly a negative effect with 5-FU.  That said, one chemotherapy combination that seemed especially promising has been shown to cause serious cardiac issues.

And in general, one of the important issues with herceptin is that it can have serious effects on the heart .

What are the side effects?

The most common side effects of herceptin are: fever, chills, and lose of strength.  Cardiac dysfunction is also not uncommon, but the exact rate is unclear.

One study that looked at treatment combining herceptin with anthracylcines (like doxorubicin) showed a surprising 27% rate of heart issues, versus 8% in those treated with anthracylcines alone, which are themselves bad for the heart.

A study that looked at treatment with herceptin alone as a first-line option showed a much lower 2.6% rate of cardiac incident, which went up to 4.3% when it was used as a second/third-line treatment.

As such, it is likely that herceptin should not be given alongside anthracyclines.

Rare side effects of herceptin include hypersensitivity reactions, pulmonary issues like dyspnea and pulmonary infiltration.  As always, the benefits of the medication should be weighed against its potential cons.

Sources:

Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer
The development and clinical use of trastuzumab (Herceptin)



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This post was written by on Tuesday, December 22, 2009. This author has written 223 posts on this blog and has 4934776 total posts views.


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5 comments

  1. I was recently diagnosed with HER2/NEU: 3+ strong positive breast cancer and have been prescribed for Herceptin.
    In addition to high costs, I am worried about heart related side effects.
    I wonder if someone who has gone through the hercepting treatment in the past can share her experience.

  2. I have been on herceptin for over 6 1/2 years, it has saved my life. I had a rapid spreading breast cancer that went to the bone resulting in both hips being replaced. As it went to the bone I will be on it for the rest of my life. All I can say is that it is working, I’m still alive. Actually except for the fact I have cancer and will always have it (once in the bone, forever in the bone) I am basically healthy. I have echos of the heart and my last one showed no change so to date it has not affected my heart. I have infusions every 3 weeks and because they knew from the start I would be on it long term, I had a port inserted so don’t have to worry about vein problems. Thankfully my insurance has covered the costs. Attitude has a lot to do with recovery, my mantra is ‘I don’t have time for this’. So go for and good luck to you, I’ll pray for you and hope that you have the great results that I have had, not to mention I have a great doctor. His treatment program has been everything for me.

  3. I have been o. Herceptin over 6 years, nearly 7 in combination with femara pill. I can not imagine getting off of it. It would feel like jumping off a cliff without a parachute. My dr. Today asked if I would consider getting off the herceptin, I shrugged, my theory is, I am a stage4 breast cancer survivor and my lifeline is the herceptin . As for my heart, I have echo done every 3 months, and I am told that if I should have heart damage from herceptin, it is almost always reversible .I too have infusions every 3 weeks in Miami beach. And have a port. I feel great ! I am alive and enjoying many wonderful trips with my family. So if it ain’t broke,don’t fix it. If herceptin works, don’t take me off it

  4. I have been on Herceptin for 2½ years and have felt great. I have stage IV breast cancer and without the Herceptin I believe I would not be here. I have had no side effects, but I have an Echo done every three months and so far so good. I do weekly infusion in lieu of every three weeks and it has worked very well, though without my port I believe that it would be very difficult. I believe that attitude is half the battle and a positive attitude and lots of prayer has kept be going and I hope it will be so for years to come. So if you have to be on Herceptin for life it is not nearly as bad as the alternative. Live, Love and be Happy

  5. I have stage 4 BC with liver mets. I have been on herceptin almost 1 1/2 years and currently my cancer is “inactive”. Overall I feel prettty good but have never completely regained my strength or energy. Just wondering how other lifelong herceptin patients’ energy levels,etc. are and if they’ve changed their lifestyles? I am struggling with how to manage work or whether to go on disability. I would appreciate hearing from anybody with similar issues. Don’t know anyone with in my situation…..

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