Twenty years ago, no targeted treatments existed for breast cancers with high levels of a protein called HER2 (HER2-positive, or HER2+). The significance of HER2 in breast cancer had only been recognized in 1987, when excessive levels of the protein were identified in about 20% of breast cancers. Oncologists realized that high levels of HER2 mark a type of cancer with a poor prognosis, as compared to the predominant type of breast cancer: estrogen receptor-positive, HER2 negative (HER2-).
The possibility of targeting HER2 to treat cancer was fulfilled in 1998, when the U.S. Food and Drug Administration (FDA) approved Herceptin (generic name trastuzumab), for treatment of metastatic HER2+ breast cancer. Made by Genentech, Herceptin is a type of drug known as a humanized antibody, meaning that it mimics an immune system attack on tumor cells, specifically those with high levels of HER2. Now, 20 years later, it is easier to appreciate the significance of this drug, which literally changed the lives of many HER2+ breast cancer patients, and continues to do so today. Continue reading…
Originally from the U.S., Ellen McGregor Kortan and her husband saved carefully and retired early so they could travel the world. They had been globetrotting continuously for three years when Ellen was diagnosed with breast cancer at the age of 46. We emailed her some questions about her nomadic cancer experience, which she answered while en route from Athens to Singapore:
You and your husband describe yourselves as retired budget travelers. What does that mean?
We saved money and lived below our means for many years, so that we could travel before we got too old or too sick for continuous globetrotting. We can afford this lifestyle if we stick to a budget. We live like we lived at home, but now it’s in other countries, typically where our dollars go further.
What was your initial diagnosis, and where were you at the time?
I was diagnosed with ductal carcinoma in situ, or DCIS, commonly called Stage 0 cancer, in Split, Croatia. Cancerous cells were trapped in a milk duct and were not yet invasive, according to the sample analyzed from a stereotactic biopsy. The DCIS covered a large area relative to the size of my breast, and so doctors recommended a mastectomy.
Based on family history, I had a double mastectomy. The pathology report from that operation revealed a tiny invasive tumor in the DCIS area – it measured just 1.5 millimeters. The tiny tumor upstaged my case to Stage 1 breast cancer.
Your case was considered “medically interesting.” How did that influenced your treatment options?
My tumor was so tiny, it’s not common to come across that size. Usually when invasive cancer of my type is found, it’s larger, although radiologists say they are seeing more cases as imaging and detection improve. My tumor was also triple positive, so it was considered aggressive. There is no clear standard of care for tumors of this type and size. This is why my case was called “medically interesting.” There are no right answers – or presumably wrong answers – for treatment for this size and type of tumor. My sentinel node was negative.
The National Comprehensive Cancer Network (NCCN) guidelines, which are used around the world, say patients with node negative, HER2-positive tumors under 10 millimeters should “consider” chemotherapy and trastuzumab (Herceptin), but smaller than 10 millimeters is “unlikely” to require chemotherapy. Anything larger than 1 centimeter gets chemotherapy and Herceptin as standard treatment (see chart 4.2).
Guidelines by the European Society for Medical Oncology (ESMO) make it more confusing – they’re even more “strict,” if you will, than in the U.S. The ESMO guidelines state all patients with node-negative, HER2-positive tumors should get chemotherapy and Herceptin, “except possibly T1a lesions.” T1a is a tumor size classification – 1 to 5 millimeters.
Who did you consult about your treatment options, and what was your initial approach?
I had a bilateral mastectomy in Zagreb, Croatia. In that city, I saw two oncologists who gave completely different treatment recommendations. One of those oncologists was fascinated by my “medically interesting” case and sent it to his colleagues in the European Union, where a panel of three oncologists weighed in. I had another panel of three oncologists from San Francisco weigh in, and they also were divided. The ninth opinion came from my mother’s oncologist in New York.
The opinions ranged from doing nothing beyond the bilateral mastectomy, to taking tamoxifen and skipping other drugs, to taking Herceptin without chemotherapy, to taking Herceptin with chemotherapy.
You also reached out for guidance from ASK Cancer Commons. How did you hear about us?
I joined some Facebook groups for breast cancer support. Getting breast cancer is a horrible thing and I was away from my support network. I also wanted to learn everything I could about my type of cancer, and see if there was any woman who might be remotely like me – receiving breast cancer treatment abroad. In one of those groups, someone suggested I contact Cancer Commons for yet another opinion. I had never heard of the organization before. By that point, I had nine opinions, and was leaning towards a treatment decision, but still was not fully comfortable with it. I was maybe 85.7 percent of the way there. Cancer Commons was officially my tenth opinion.
How did Cancer Commons help you?
Cancer Commons helped give me peace of mind with my treatment decision. Chief scientist Emma Shtivelman’s expert, science-based opinion made such logical sense, and it also felt right in my soul. I’d already been leaning heavily towards a decision, and Emma helped me achieve the final decision. In the end, I decided against Herceptin with or without chemo – without regard for cost or travel, but based simply on the research and expert opinions available to me at the time I made my decision. I am on tamoxifen for the foreseeable future.
But Emma’s more than a scientist. She is a caring person. I reached out to her after my decision for help. She reviewed my summaries on a small website I created to help other people with HER2-positive tiny tumors. The site is mainly a collection of studies somewhat related to that type and size of tumor. There are no studies designed specifically for patients with sub-centimeter HER2-positive tumors – a reason why treatment decisions in cases like mine also are “medically interesting.”
Most medical professionals, as caring as they may be, likely wouldn’t take the time to review a laywoman’s summaries on a blog site dedicated to help patients with HER2-positive tiny tumors. But Emma did. Since September, four women with tumors like mine have reviewed the studies linked on this blog site. I’m thrilled over that. Most newly diagnosed patients don’t have enough time or energy to find this material and read it after a shocking diagnosis. Since I’m early retired, I made the time.
How has being a retired budget traveler influenced your cancer care?
I did not expect health care to be so good outside the U.S. At the same time, finding great, English-speaking doctors is the biggest challenge. For example, I found a highly regarded surgeon in Croatia to perform my double mastectomy without reconstruction. He came recommended by other doctors, and he had a great portfolio. He did a fantastic job from what I can tell. Compared to prices in the U.S., the cost of my surgery was totally reasonable.
It might sound easy, but it takes fortitude to deal with the process. Another example: the Croatian pathologists wrote my mastectomy report in their native language, and sometimes things are lost in translation, so the phrase “breast with goat hair” appears on my Google-translated version. As a breast cancer patient in a foreign country, I can either cry and go home, or laugh it off and realize it’s just one phrase, and the important stuff is implicitly clear – such as the size and features of the tumor.
How has breast cancer influenced your plans as a retired budget traveler?
We are working out future plans. We were not required to buy health insurance this year because we were not going to be in the U.S. For next year, we expect to be in the U.S. later in the year, and so we likely will buy insurance. But it’s worth pointing out that so far, my experience with health care abroad has been excellent, and relatively affordable if forced to pay out-of-pocket in a country with reasonably priced health care. The cost for my double mastectomy was about $3,500 – lower than some U.S. deductibles. That price was only for the surgery. The pathology tests, biopsy, and mammogram were additional costs that also were reasonable.
If I had needed chemotherapy, we would have stayed in Croatia under a medical visa through treatment. If I had decided to take Herceptin, we would have bought the subcutaneous form in oncology offices in different countries. We actually had a plan on what European countries we would visit based on a self-injection schedule of every three weeks. (Self-injections are available in Europe.) My surgeon was ready to help by calling colleagues throughout the EU. Our plans would have been changed, but our retired budget travel dreams could still be realized.
What comes next for you?
I’m responding to your questions on a flight from Athens to Singapore. Next month, we will be in Kuala Lumpur, Malaysia, and it will be six months since my initial diagnosis. I am about to start my search for highly regarded doctors in Kuala Lumpur for my needed checkups. I feel great, and our plan is to move beyond the six-month mark and continue traveling around Southeast Asia for the foreseeable future.
What advice would you give to someone who is newly diagnosed with breast cancer?
Get a second opinion, and maybe a third or a fourth, too, even if your cancer case is more common than mine. Don’t be rubber-stamped through treatment. Cancer Commons is an amazing free service that helped give me peace of mind with my ultimate treatment decisions.
Also, hang in there. A breast cancer diagnosis is not easy. You’re about to go on a journey that will change you. Give yourself time to process everything. Give yourself plenty of extra care, and respect.
Is there anything else you’d like to share?
There are no absolute answers when it comes to dealing with cancer treatment – only probabilities based on the experiences of different people with similar cancers. But I absolutely know this: I made the best decision I could and I’m comfortable with it.
You hear the phrase, “you only live once,” and it registers. You logically know it to be true. But cancer changed my understanding of that cliché. Life is now, not later, and so I’ll live the best life I can – right now.
Super Patients are cancer survivors who learned to be more engaged in their own care. Cancer Commons believes every patient can be a Super Patient or benefit from a Super Caregiver or Super Advocate. We hope these stories will provide inspiration and hope for your or your loved one’s own treatment journey.
“Adding to a growing list of similar results, the Short-HER study was unable to show noninferiority of 9 weeks of trastuzumab compared with the standard 1 year when given along with chemotherapy in women with HER2-positive breast cancer. Shorter administration does, however, reduce the risk of cardiotoxicity.
” ‘Adjuvant pivotal trials with 1-year trastuzumab have significantly improved the prognosis of HER2-positive early breast cancer,’ wrote study authors led by Pierfranco Conte, MD, of the Istituto Oncologico Veneto in Italy. Several studies have attempted to reduce the duration of trastuzumab, though most have failed to show noninferiority.”
“Outcomes for patients with HER2-positive breast cancer did not differ when treated with sequential chemotherapy plus trastuzumab compared with a concurrent approach, according to a new phase III trial.
” ‘The effectiveness of trastuzumab with chemotherapy in the neoadjuvant setting is evident; however, the cardiac safety of trastuzumab combined with anthracyclines has been questioned,’ wrote study authors led by Kelly K. Hunt, MD, of the University of Texas MD Anderson Cancer Center in Houston.”
“Tucatinib used in combination with capecitabine, trastuzumab (Herceptin), or both agents showed promising antitumor activity in heavily pretreated women with HER2-positive breast cancer with or without brain metastases, according to findings published in The Lancet Oncology.
“In phase Ib results from a nonrandomized, open-label study, 83% (5/6) of patients with measurable disease treated with tucatinib/capecitabine had an objective response, as did 40% (6/15) of patients receiving tucatinib/trastuzumab. Sixty-one percent (14/23) of patients treated with the combination of all 3 drugs had an objective response.”
“The adjuvant treatment landscape for patients with HER2-positive breast cancer continues to grow, particularly following the recent FDA approval of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy, which was based on findings from the APHINITY trial.
“In the phase III trial, the combination demonstrated a 3-year invasive disease-free survival (DFS) rate of 94.1%, which represented an 18% reduction in the risk of developing invasive disease or death. The benefit was more pronounced among higher-risk patients. The DFS rate for patients with node-positive disease was 92.0% with pertuzumab versus 90.2% with standard therapy.”
“A combination of pembrolizumab (Keytruda) and trastuzumab, tested in patients with trastuzumab-resistant advanced HER2-positive breast cancer, was well tolerated and had clinical benefit in patients whose tumors were positive for a biomarker for pembrolizumab, according to data presented from the phase Ib/II PANACEA trial at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5–9.
“ ‘We wanted to investigate if immunotherapy approaches can work in patients with advanced HER2-positive breast cancer that is resistant to trastuzumab,’ said Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, working with the International Breast Cancer Study Group (IBCSG).”
“A new randomized trial found that neoadjuvant trastuzumab/pertuzumab alone yields a substantially worse rate of pathologic complete response compared with trastuzumab/pertuzumab plus paclitaxel in women with early, HER2-positive, hormone receptor (HR)-negative breast cancer.
” ‘Pathologic complete response (pCR) after neoadjuvant [therapy] has strong prognostic impact in HER2 disease,’ wrote study authors led by Ulrike Nitz, MD, of the West German Study Group GmbH in Moenchengladbach, Germany. The WSG-ADAPT HER2+/HR− trial assessed whether dual blockade with trastuzumab and pertuzumab could achieve similar rates of pCR in those with strong early response to dual blockade along with chemotherapy.”
Non-metastatic breast cancers are most often treated with surgery, but if the tumors are fairly large, or involve nearby lymph nodes, neoadjuvant (pre-operative) treatments with chemotherapy (NAC) are done first. NAC often reduces the tumor size and kills cancer cells in lymph nodes, if present, prior to surgery, improving the outcome. The best possible result of neoadjuvant treatment is pCR (pathologic compete response), when the tumor is no longer visible in imaging studies. Here, I review the new directions in which neoadjuvant treatments are evolving.
Today, treatments for metastatic breast cancers are tailored for specific subtypes. Starting with the introduction of the drug trastuzumab (Herceptin) for HER2-positive cancers, new, more specific treatment options were eventually developed and approved for other types as well. Estrogen deprivation endocrine therapies, lately prescribed in combination with CDK4/6 inhibitors, are used in estrogen receptor (ER)-positive cancers. Triple negative cancers (TNBC) are still treated mostly with chemotherapy, but immune checkpoint drugs and PARP inhibitors are explored in clinical trials, with some successes reported.
However, neoadjuvant treatments (except for HER2+ cancers) remain largely limited to chemotherapy regimens. This is starting to change now, with new approaches tailored to the cancer type being investigated in clinical trials.
In this regard, it is important to mention the I-SPY2 trial, NCT01042379, which started in 2010 and is for women with stage II-III breast cancer. It offers about a dozen drugs that are chosen based on particular features of the newly diagnosed cancers. This trial has a unique design and has produced some important results. Additional treatments and trials for various types of breast cancer are discussed below. Continue reading…