The Internal Enemy | Climax

Shared decision-making

(Fictional narrative by the doctor)

James Fleck, MD, PhD & João A de Andrade, MD

Anticancerweb 10 (01), 2019

It was very early in the morning when Ruth was brought into the operating room. 

Despite being a clinical oncologist, I am usually present in the operating room for my patient’s surgery.  I always enjoy to watch how the team performs like a well-tuned orchestra… On that particular morning, the “orchestra” consisted of six physicians (one anesthesiologist, one radiologist, one pathologist, two surgeons and myself), who had been working together for more than twenty years. 

Each member of the team already knew all the details of Ruth’s case. The radiologist took care of the tumor needle-wire localization the day before; the anesthesiologist conducted a long interview and performed a complete physical examination; the pathologist reviewed the slides of the previous biopsy material, confirming the morphologic diagnosis, and the surgeon showed her an educational video with the highlights of the procedure about to take place. 

Lights on! The surgery begins…

The resection was carefully performed outside the wires, taking in to account that they were orthogonally positioned at least 1 cm away from the primary tumor margins. Since the lesion was located in the upper outer quadrant, the surgeon decided for a lateral mammoplasty, which he felt would give Ruth the best cosmetic results.

The resected tissue, including the wires, was sent to the Department of Radiology where the image was analyzed based on the two previous orthogonal mammograms. This step was performed to ensure that the resection margins were tumor-free. 

Digital images were then sent back to the operating room, where the radiologist compared the mammograms with a previous breast MRI. This is a second layer of confirmation that all the cancerous lesion had been removed with at a margin of normal tissue of at least 1 cm. Additionally, the surgical specimen was marked with stitches at the superior and medial aspects to better orient the pathologist during the definitive assessment of the tissue.

The second phase of her surgery would be the axillary lymph node sampling. The surgeon used a dual technique, injecting both blue dye and a radioactive colloid close to the area where the tumor was previously located. The tracers were caught by the lymphatic vessels and drained into the axillary lymph nodes. Sentinel lymph nodes are those that first receive the injected tracers.  This technique allows the surgeon to not only visually locate the node that has the blue dye but also to use a probe to identify the node that has a higher level of radiation from the second tracer.  This approach leads to a very low rate of false negative results. The absence of tumor cells in the sentinel lymph nodes predicts the absence of any additional distal axillary lymph node metastases in 95% of the cases. 

The resected lymph nodes were handed to the pathologist. 

This is always a very tense moment.

The surgeon put the procedure on hold waiting for the pathologist report. After a few minutes, the pathologist came back with the news. He had identified three sentinel lymph nodes. Two were negative, but unfortunately one had a few tiny tumor cell clusters that he would need to better evaluate later on using a more refined technique that could not be performed in the small histology laboratory of the operating room.

At this moment, the surgeon looked at me and, after a brief discussion, there was agreement that we should not move forward with a complete axillary lymph node dissection. The rationale was nuanced.  Since Ruth’s primary tumor was almost 2 cm and she would have a breast conserving surgery followed by a whole-breast irradiation, it sounded reasonable to not submit her to a procedure that could be associated with functional and aesthetic distress. The axillary lymph node dissection would be necessary if three or more lymph nodes had shown metastatic cells.

The surgery was now finally over.

Two weeks later, Ruth came back to my office.

She had an uneventful recovery, requiring only two days in the hospital and we were able to remove the surgical drains just before her discharge. Her right breast showed only a little swelling, but no bruises or signs of infection. She was feeling well, describing just a little limitation in rising her right arm, but no pain. She was coping well from an emotional standpoint. 

Ruth felt a sense of relief after having the tumor removed from her breast. She knew the treatment was not over, but she realized that from that moment on she would be dealing only with microscopic disease.

Ruth had already been informed about the presence of cancer cells in one of the sentinel lymph nodes. She also understood that we would be getting additional, more detailed, results from the Department of Pathology. They were performing a technique called immunohistochemistry to better evaluate the extension of the disease inside of the lymph nodes.  

The day before Ruth’s follow up appointment, I received the pathology report. The lumpectomy was successful. All the margins of the surgical specimens were at least 1 cm away from the primary tumor. The primary tumor measured 1.8 cm, which was less what the imaging tests had suggested. However, one of the three sentinel lymph nodes had tumor cell deposits larger than 2 mm. Ruth’s disease was then staged as “pN1”, which unfortunately made her prognosis worse. 

She was surprisingly calm and did not ask me about the pathology report. She was under the impression that once her primary tumor was completely removed, there would be an automatic “downstaging” of her disease. Unfortunately, the reality was a bit more complicated and quite the opposite from her assessment. The final pathology report had, in fact, “upstaged” Ruth’s disease. The more detailed analysis of the tissue demonstrated that the initial impression of her having isolated tumor cell cluster (pNoi+) actually represented a “macrometastatic” involvement of one axillary lymph node (pN1). This finding would definitely increase the complexity and toxicity of her treatment.

I was looking for the best way to approach the subject. I had already planned all of her adjuvant treatment and I was certain that at some point Ruth would ask me for all the details.  

Ruth eventually broke the silence and asked me: How will we control the residual disease?

Well…that was my queue – she was ready!

I explained to her that she was a young woman with a high-risk Her-2 positive breast cancer, staged as T1N1M0 (stage II) who was recovering from a successful breast conserving surgery. However, as she had already anticipated, the treatment was not over as there were cancer cells in one of the axillary lymph nodes. She would have to receive systemic treatment, including chemotherapy and a dual anti-Her2 blocking agent. She would also receive irradiation of the whole right breast after chemotherapy with the goal to achieve better local control of the tumor.

She interrupted me asking for an estimation of how long the complementary treatments would take.

I answered that I anticipated that she would be under treatment for at least one year.

Ruth replied: I was reading about the side effects of chemotherapy. Most of them, such as hair loss (alopecia), nausea, vomiting and low white blood cell counts have been extensively described, but I did not find much written about cardiac risks!

Again, Ruth had identified a very delicate issue. She would receive six cycles of a combined chemotherapy regimen with docetaxel + carboplatin (DC), along with a dual anti-Her2 blockade based on trastuzumab (T) + pertuzumab (P). Safety data from clinical trials using this so-called “DCT combined protocol” report a very low incidence of (usually reversible) congestive heart failure (0.4%). Additionally, radiation therapy would be directed only to the right side of her chest, avoiding most of the area where the heart is. The survival benefit of the DCT protocol significantly outweigh the risk of cardiac adverse events. I reassured her that I had already planned to periodically evaluate her heart function using a non-invasive ultrasound test called “echocardiogram”. The echocardiogram would be able to detect early signs of impairment of the heart muscle, allowing us to adjust the treatment plan before the development of significant heart failure. 

She went on remarking: “Why should I receive so many drugs? I can understand the use of chemotherapy, but why should I receive a dual anti-Her2 blockade?”

I was expecting this rationale challenge and also knew that Ruth was well-prepared to understand the answer. I explained that the suffix mabappearing in both anti-Her-2 drugs means a monoclonal anti-body (MoAb) against the receptor Her-2 expressed in her tumor cells. The two MoAb would act complementary: trastuzumab would bind to the extracellular domain of Her2 receptor and pertuzumab would prevent Her2 dimerization, both blocking the signaling transduction pathway and decreasing tumor cell proliferation. The addition of trastuzumab to chemotherapy for cases like Ruth’s is well established and supported by evidence from a metanalysis of multiple clinical trials. The addition of pertuzumab is supported by one recent randomized clinical trial, showing a 92% three-year disease-free survival among Her2 + breast cancer patients that had lymph node involvement by the disease (N1).

Ruth sighed in relief! Although she had not been asking me about prognosis, I knew that she was happy to hear the phrase “92% disease-free survival”.

Ruth continued to be very proactive. She had already read most of the available literature regarding chemotherapy-induced alopecia. She knew about scalp hypothermia minimizing the risk of alopecia, but ultimately decided against it. She mentioned that her health insurance would not cover neither the device nor the necessary extra time during chemotherapy infusion. She decided to immediately change to a short hair style, to minimize the psychological impact of hair loss that usually comes three weeks after the first cycle. She also ordered a wig that almost perfectly matched the color, thickness and style of her natural hair. At this point, she had also mastered the literature about the new drugs used to block chemotherapy-induced nausea and vomiting. 

Ruth was very committed to minimize the impact of the treatment on her life style. 

She planned to keep her job as a teacher, having worked out a flexible schedule with her supervisor.

We were about to wrap-up the appointment when suddenly my phone rang. 

It was my secretary advising me that Ruth’s mother and her two daughters were waiting for her at the reception.

Ruth had arranged a visit to the treatment area to get acquainted with the environment and to get to know the nurses and the pharmacists. Ruth invited her mother and her two daughters to join her. Her mother, Juliet, was a very affectionate 65-year-old lady, entirely committed to supporting Ruth through her battle. Her two daughters, Samantha and Lisa. were lovely young ladies, who were nine and eleven years old, respectively. Both were very polite and acted very mature for their age.

I praised Ruth for the idea of meeting the treatment team and my secretary took care of the introductions. The treatment area nurse was very experienced and took the time to describe all the steps of the treatment in a very detailed and compassionate way. During the planned intravenous infusion sessions, Ruth would seat on a comfortable chair and her family would be allowed to stay with her. All drugs would come to the clinic ready to be infused after being mixed and labeled by the pharmacists. All this detailed information was very reassuring to Ruth and her family. They felt safe and supported by a multidisciplinary team that worked under very strict protocols.

They also mention that they were somewhat surprised with the feeling that the environment did not feel cold or hostile. On the contrary, the treatment area felt welcoming, comfortable and relaxed. By the end of the visit, Ruth and her family were ready and confident to get started!

 Sometimes the worst internal enemy is the imaginary one!

 To be continued in PLOT 5 (falling action): Genetic counseling… 

*     Attention: The story 1 was published sequentially from the PLOT 1 to the PLOT 6, however it will appear backwards. So, you will always see the most recent publication. Just browse in numbered pages located at the bottom of the homepage and start to read story 1 from the beginning. 

© Copyright 2019 Anticancerweb

 James Fleck, MD, PhD: Full Professor of Clinical Oncology at the Federal University of Rio Grande do Sul, RS, Brazil 2019

Joao A. de Andrade, MD: Professor of Medicine and Chief Medical Officer, Vanderbilt Lung Institute, Vanderbilt University Medical Center, Nashville, TN – USA 2019 (Associate Editor)