Biology Has Spoken

There are some moments in life you’ll never forget. In my 25-year career as an oncologist I’ve attended hundreds of conferences and I’ve listened to and presented the results of many clinical trials. I’ve been excited to see the advances we’ve made in the fight against cancer and tremendously disappointed by the times when we have tried and failed. But there’s one conference, in particular, that will always stand out in my mind.

In May 2005, while practicing oncology at Mayo Clinic, I attended the American Society of Clinical Oncology (ASCO) meeting in Orlando, Florida, along with some 25,000 other cancer specialists from around the world. That year, there were 3,800 papers presented in poster sessions and panel discussions, most about incremental improvements in care and treatment. With cancer, we’re used to small steps and big hopes.

But this year I was excited. I was presenting data that I believed had the potential to change the treatment landscape of HER2-positive breast cancer – an aggressive form of the disease that affects 15-20 percent of patients.1 Genentech had developed a targeted treatment, called Herceptin® (trastuzumab) Indication and Important Safety Information, which is designed to block the signals that cause HER2-positive cancer cells to grow and divide. It was already approved in combination with paclitaxel chemotherapy to treat people with later stage HER2-positive breast cancer that had spread to other parts of the body.2 But at that incurable stage of the disease, we could only hope to extend the lives of patients. The next big test was to see if Herceptin could help prevent the cancer from coming back in people with early HER2-positive disease, where there’s an opportunity to delay the spread of the cancer or perhaps even prevent it from returning altogether.

There were no guarantees and there were also plenty of skeptics. So many of us had seen medicines succeed and fail in different stages of the same type of cancer. That’s the complex and challenging nature of this disease.

There was an electric, uplifting atmosphere and a sense of anticipation.

As I walked into the large conference hall, I was moved to see how crowded it was — friends, investigators and collaborators filled the seats, and even more were standing in the back. There was an electric, uplifting atmosphere and a sense of anticipation. Up at the podium, I scanned the crowd and spotted one of my patients who had participated in the trial. She gave me a warm smile, which was incredibly touching and reminded me that while I was presenting numbers and statistics, I was actually talking about women just like her. I took a deep breath.

“Adding Herceptin to the chemotherapy regimen,” I told the group, “reduced the risk of breast cancer coming back by half compared with women who received chemotherapy alone.”3 While there are serious risks associated with taking the medicine, including a potential for heart failure, the safety of the medicine was consistent with what we had seen in previous Herceptin clinical trials.3 The results showed 85 percent of people who received Herceptin and chemotherapy in the trial were free from disease after four years compared with 67 percent of women treated with chemotherapy alone.3 The huge audience was quiet as the significance of those numbers settled in. We oncologists hadn’t seen that kind of advance in breast cancer treatment in 30 years. Indication and Important Safety Information

At the close of the session, George Sledge, Jr., who is now Chief of Oncology at the Stanford University School of Medicine, said that the results marked a significant new era for breast cancer care. “Biology has spoken,” he told the group, “and we should listen.”4


Used with permission. © 2005 American Society of Clinical Oncology. All rights reserved.

George W. Sledge Jr. at ASCO 2005. Reproduced from Rabiya S. Tuma. Journal of the National Cancer Institute (2005) 97 (12): 870-871 (George W. Sledge Jr. and Edith A. Perez). By permission of Oxford University Press.

The room erupted in applause, and everyone in the audience jumped to their feet for a standing ovation. They weren’t just standing up for the investigators, but for the patients, their loved ones, their doctors, and for this significant scientific advancement. What was so wonderful about the moment was that everyone in the room felt that they were part of something special, and that we all did it together.

It was an emotional moment, one that no one in that room will ever forget. Everyone was congratulating each other, hugging, smiling, and rushing the podium—all of which was entirely out of character for that normally cool and sober crowd. It made me feel not only deeply happy, but humble, to be part of something that most physicians and investigators never have a chance to experience in their lifetimes.

In November 2006, the Food and Drug Administration approved Herceptin for treating early-stage HER2-positive breast cancer when given with chemotherapy (doxorubicin, cyclophosphamide and paclitaxel) after surgery.2 The data were significant in the context of patients’ lives and impacted the practice of HER2-positive breast cancer care in the U.S. and around the world. Since then, we’ve seen a significant improvement in overall survival: Adding Herceptin to chemotherapy was shown to reduce the risk of death by more than one-third.2 In January 2008, it was also approved as a stand-alone medicine following anthracycline-based chemotherapy. Herceptin carries a boxed warning for serious cardiac risks associated with the medicine, as well as potential infusion reactions, risk for severe lung problems, and the potential to harm an unborn baby. Indication and Important Safety Information

As physicians, we aspire to improve the duration and quality of the lives of our patients. That’s pretty profound at an individual level. But when you participate in a study like this, which has translated to impacting so many thousands of lives, well that’s it. That’s a big moment.


Read the full story behind Herceptin and Genentech’s other HER2-targeted medicines here.

What it Treats

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early-stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2+) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature.* Herceptin can be used in several different ways:

  • As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as “ACTH
  • With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as “TCH
  • Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin) based therapy (a type of chemotherapy)

Patients are selected for therapy based on an FDA-approved test for Herceptin

*High-risk is defined as ER/PR-positive with one of the following features: tumor size >2 cm, age

Metastatic Breast Cancer

Herceptin has 2 approved uses in metastatic breast cancer:

  • Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer
  • Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease

Patients are selected for therapy based on an FDA-approved test for Herceptin

Gastric Cancer

Herceptin is approved, in combination with chemotherapy (cisplatin and either capecitabine or 5-fluorouracil), for the treatment of HER2-positive metastatic cancer of the stomach or gastroesophageal junction (where the esophagus meets the stomach) in patients who have not received prior treatment for their metastatic disease.

Patients are selected for therapy based on an FDA-approved test for Herceptin.

Important Safety Information

Possible Serious Side Effects With HERCEPTIN

Not all people have serious side effects, but side effects with HERCEPTIN therapy are common.

Although some people may have a life-threatening side effect, most do not.

Your doctor will stop treatment if any serious side effects occur.

HERCEPTIN is not for everyone. Be sure to contact your doctor if you are experiencing any of the following:

HEART PROBLEMS

These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both HERCEPTIN and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. Your doctor will check for signs of heart problems before, during, and after treatment with HERCEPTIN.

INFUSION REACTIONS, including:

  • Fever and chills
  • Feeling sick to your stomach (nausea)
  • Throwing up (vomiting)
  • Pain (in some cases at tumor sites)
  • Headache
  • Dizziness
  • Shortness of breath

These signs usually happen within 24 hours after receiving HERCEPTIN.

Be sure to contact your doctor if you:

Are a woman who could become pregnant, or may be pregnant

HERCEPTIN may result in the death of an unborn baby or birth defects. Contraception should be used while receiving HERCEPTIN and for 7 months after your last dose of HERCEPTIN. If you are exposed to HERCEPTIN during pregnancy or within 7 months after your last dose of HERCEPTIN, you should immediately report HERCEPTIN exposure to Genentech at 1-888-835-2555.

Have any signs of SEVERE LUNG PROBLEMS, including:

  • Severe shortness of breath
  • Fluid in or around the lungs
  • Weakening of the valve between the heart and the lungs
  • Not enough oxygen in the body
  • Swelling of the lungs
  • Scarring of the lungs

Your doctor may check for signs of severe lung problems when he or she examines you.

Have LOW WHITE BLOOD CELL COUNTS

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving HERCEPTIN plus chemotherapy than in patients receiving chemotherapy alone.

Your doctor may check for signs of low white blood cell counts when he or she examines you.

Side Effects Seen Most Often With HERCEPTIN

Some patients receiving HERCEPTIN for breast cancer had the following side effects:

  • Fever
  • Feeling sick to your stomach (nausea)
  • Throwing up (vomiting)
  • Infusion reactions
  • Diarrhea
  • Infections
  • Increased cough
  • Headache
  • Feeling tired
  • Shortness of breath
  • Rash
  • Low white and red blood cell counts
  • Muscle pain

Some patients receiving HERCEPTIN for metastatic stomach cancer had the following side effects:

  • Low white blood cell counts
  • Diarrhea
  • Feeling tired
  • Low red blood cell counts
  • Swelling of the mouth lining
  • Weight loss
  • Upper respiratory tract infections
  • Fever
  • Low platelet counts
  • Swelling of the mucous membranes
  • Swelling of the nose and throat
  • Change in taste

You should contact your doctor immediately if you have any of the side effects listed above.

You are encouraged to report side effects to Genentech and the FDA. You may report side effects to the FDA at 1–800–FDA–1088 or http://www.fda.gov/medwatch.

You may also report side effects to Genentech at 1–888–835–2555.

Please see additional select Important Safety Information throughout, and the accompanying full Prescribing Information, including Boxed WARNINGS.


Title Photo: Edith A. Perez at ASCO 2005. Reproduced from Rabiya S. Tuma. Journal of the National Cancer Institute (2005) 97 (12): 870-871 (George W. Sledge Jr. and Edith A. Perez). By permission of Oxford University Press.

1. Wolff AC, et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol 2013;31(31):3997-4014.
2. Herceptin [package insert]. South San Francisco, Calif.: Genentech, Inc. 2017.
3. Genentech. Herceptin Plus Chemotherapy Improved Disease-Free Survival and Overall Survival in Adjuvant Setting for Early-Stage Her2-Positive Breast Cancer Patients. May 13, 2005. Retrieved May 9, 2017 from http://www.gene.com/media/press-releases/8429/2005-05-13/herceptin-plus-chemotherapy-improved-dis
4. Tuma RS. J Natl Cancer Inst (15 June 2005) 97 (12): 870-871.