A Tale of Two Women, HER2-Positive Breast Cancer, and Clinical Trials

A Tale of Two Women, HER2-Positive Breast Cancer, and Clinical Trials

Don S. Dizon, MD, FACP, FASCO

Aug 29, 2013
Joan was 42, married, but appeared to be younger than that. Her husband was with her when we first met, as was her beautiful two-year-old son. “We couldn’t get a baby sitter, if you can believe that!” she said.

Sarah was 38 and was also married. She and I were closer to the same age, which was not lost on either of us. She had three kids, but did not bring them to our first meeting; she was only with her husband and he held her hand throughout that first visit. “I don’t know what I’d do without him,” she said through misty eyes.

I saw both of them around the same time, as consults regarding adjuvant therapy. Each had found a breast lump on self-exam, undergone a biopsy, and had surgery for newly diagnosed invasive breast cancer. Joan’s tumor was hormone receptor-negative, while Sarah’s was hormone receptor-positive. However, both of their tumors were HER2-positive. They each had a similar tumor stage as well; their tumors were over 2cm in size and both had node-positive disease.

Even now, I recall the lengthy discussions I had about treatment--the value of chemotherapy (and endocrine therapy in Sarah’s case), and the various combinations that could be used. Because each had HER2-positive breast cancer, I also discussed the role of trastuzumab, which, at that time, was only being used to treat metastatic breast cancer.

As it turned out, our institution was also participating in NSABP B-31, the randomized trial that evaluated standard combination chemotherapy with or without adjuvant trastuzumab. I remember giving them a consent form to participate on this trial and that I had sent them home to digest everything we discussed, to think about whether they wanted to participate in this study.

When both women returned, both of them asked me the same question: “What do you think I should do?”

“Given your cancer is HER2-positive, I would recommend treatment on the clinical trial,” I stated. “At this point, we don’t know what benefit trastuzumab will add to treatment in the adjuvant setting, and we don’t know yet what kind of toxicities it will have—both in the short term and the long term. There is a 50/50 chance you’ll get trastuzumab, but at the very least, you will receive standard chemotherapy.” It was my standard response.

Both women agreed to enroll in this trial. Following consent (and the formalities associated with registration on a clinical trial), each had undergone randomization. Joan was assigned to treatment with chemotherapy plus trastuzumab; Sarah was assigned to treatment with chemotherapy only.

We met again to review the treatment plan, and I talked with both of them about participating in this trial—making sure both of them still wanted to proceed. Joan was anxious to start, almost excited. However, Sarah admitted to being disappointed and more than a little apprehensive, because she had not been assigned to the arm receiving trastuzumab.

“Remember, Sarah, the trial is being done because there isn’t a proven benefit to trastuzumab in this setting. Remember too, your tumor expresses hormone receptors, so we have the option of endocrine treatment after chemotherapy completes.”  After our discussion, she clapped her hands and looked me in the eyes.

Okay then,” Sarah said. “Let’s get going.”

Each tolerated treatment well, experiencing few side effects and each greeted the end of therapy with a sense of accomplishment, if not relief—especially Joan, who completed a year of trastuzumab. Both women began follow-up with me and, although each had some issues in those first six months as treatment ended, they were back to a sense of normalcy within a year of completing treatment.

A couple of years after they completed therapy, the joint results of NSABP B-31 and a similar trial, NCCTCG 9831, were reported showing a survival advantage favoring the administration of adjuvant trastuzumab; treatment reduced the risk of recurrence by over 50% and the risk of death by over 30% (1,2).

Because of these results and the resultant press it generated, I made sure to touch bases with my patients who participated on the study, including both Joan and Sarah. Joan felt relief, knowing she had received trastuzumab—so relieved she cried. “I feel like I won the lottery,” she said.

The discussion with Sarah was more subdued. I had expected her to be angry (I think it’s how I would’ve reacted). But, Sarah wasn’t; although disappointed she did not receive trastuzumab, she was looking well past adjuvant treatment by then. “Well, it was a 50/50 chance, right?” she said.

We talked about whether it made sense to initiate trastuzumab now. Although the protocol allowed some women who did not receive trastuzumab to get it on the study, she did not meet the criteria to receive it; she had done too well and was well into follow-up for too long for it to classify as “adjuvant” treatment. On a personal level, she could not fathom returning to the infusion unit for an additional year of therapy. Therefore, we decided to resume follow-up.

Then Sarah relapsed, with cancer in her bones and liver. She met the news with fear and sadness; her husband was devastated. They cried in my office, wondering about an uncertain future and about time. As in our first meeting, they held hands the entire time.

“Sarah, you are not dying,” I said. “If I thought you were, I’d tell you, and if that time comes, I will. But right now, the cancer is treatable and since you have no symptoms from this cancer and are healthy despite it, you have options. And we have trastuzumab. I am optimistic I can help you live, and live well.”

But for how long?” she asked. It was her only question that day.

Sarah embarked on treatment for metastatic breast cancer, which was a journey that spanned over six years. In that time, she saw her last child graduate high school, buried both her parents, and had travelled extensively. The use of anti-HER2 agents regimens kept her disease in check while allowing her to live well.

That is, until her cancer began to show signs of drug resistance. Despite multiple attempts at treatment, her tumor had become less responsive, and started to progress despite therapy. When she came in with pain and jaundice, I feared she was had entered a terminal phase. I admitted her to the hospital and we did an urgent CT scan. Unfortunately, it showed her liver was almost entirely placed with cancer.

 “Sarah, it’s time,” I told her.

I know,” she said.

As we discussed hospice, I told her and her husband what an honor it had been to be her doctor, to get the chance to know them as people, to meet their families. “I don’t know how long you have, but I wanted to tell you that,” I said. We chatted some more, cried together, and confirmed our plans for her to be home. It was where she wanted to live and where she wanted to die.

On one of my last visits with her, I asked Sarah if she regretted participating in the clinical trial. “No, I don’t have any regrets. I knew what I was getting in to and that there were no guarantees about whether or not I’d be assigned to treatment with trastuzumab, let alone if it would work. If it helps women with breast cancer in the future, then it was worth it.”

Sarah died shortly after, in the environment she had wanted—at home, surrounded by her husband, grown children, and many friends.

Joan’s course was dramatically different. Despite having hormone receptor-negative disease, her cancer did not return. She would see me every three months, then every six months. Each time, her child was with her and in a way, I tied Joan’s survivorship to the growth and development of her son who went from a toddler sitting on mom’s lap to an active little boy, fascinated with my stethoscope. We eventually reduced her visits to oncology and I saw her only at annual follow-ups.

At her last visit, I asked if she had any questions. “No questions,” Joan said. “Just a thank you for the chance to be on that trial. It literally saved my life.” We hugged, and she walked out of my office.

These two women come to mind as I came across a tweet that read: “I don't want to be a guinea pig, but I really want that vaccine.”

It referred to an article written by a woman living with lung cancer, reflecting on her participation in a clinical trial. In it, she candidly wrote about her thoughts, fears, and frustrations with the clinical trials process and drug development.

As I read it, I thought of all the people I’ve treated as part of a clinical trial, women like Joan and Sarah, who were not guinea pigs. Thanks to the women who participated on NSABP B-31, and other similar trials, we learned that adjuvant trastuzumab dramatically alters the natural history of HER2-positive breast cancer, and results in long-lasting remissions (dare I say, cures). Their efforts have helped the women diagnosed with breast cancer after them- especially those diagnosed with HER2-positive disease. 

I fear that words that characterize participants on trials as pets or laboratory animals reinforce a paternalistic view of medicine, where doctors are nothing more than cold-hearted scientists in white lab coats and patients are powerless, uninterested, almost “caged”. Such images diminish the significance of patients who participate on trials, their rights, and their contributions.

Ultimately, progress in cancer care requires a partnership between researchers, clinicians, and patients. None of us are above the other—it is a collaboration and requires the utmost respect and mutual trust. Therefore, I felt compelled to respond to the article and so I tweeted: 

“People who participate in clinical trials are not guinea pigs. They are trailblazers! Partners as we fight for better. #hcsm

NOTE: Names and details of both patients changed to protect privacy.


1. Romond EH, Perez EA, et al. Trastuzumab Plus Chemotherapy for Operable HER2-Positive Breast Cancer. NEJM 2005, Vol. 353. No. 16, pp. 1673-168

2. Romond EH, Suman VJ, Jeong J-H, et al. Trastuzumab plus adjuvant chemotherapy for HER2-positive breast cancer: final planned joint analysis of overall survival (OS) from NSABP B-31 and NCCTG N9831. SABCS Annual Meeting Abstracts 2012:S5-5.


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