Advances in Breast Cancer Treatment: Expert Panel Discussion of Challenging Cases

Joyce A. O’Shaughnessy, MD

Advances in the detection, diagnosis, and treatment of cancer are developing at an increasingly rapid pace. Although evidence-based medicine has led to significant progress in our knowledge, skills, and approaches to treating patients with breast cancer, the implementation of these improvements into clinical practice requires continued learning.

Staying abreast of the clinical research may be a good way to keep informed on novel agents and new treatments, but journal articles provide a one-dimensional interpretation of the findings and rarely discuss the practicalities of implementing these treatments into daily clinical practice. Scientific meetings, on the other hand, provide opportunity for interaction and an exchange of ideas. It is this kind of clinical debate where practical experiences are shared and where the discussions can ultimately facilitate the practical application of clinical data.

For this reason, Contemporary Oncology is introducing a series of discussions that highlight challenging cases presented at medical education conferences hosted by our affiliate company, Physicians’ Education Resources (PER).

The following cases were discussed at the 10th International Congress on the Future of Breast Cancer, which was held in Coronado, California, from August 4-7, 2011.

The case discussions were moderated by Joyce A. O’Shaughnessy, MD, a medical oncologist with Texas Oncology-Baylor Charles A. Sammons Cancer Center in Dallas. Other panelists included Hope S. Rugo, MD, director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center; and Frankie Ann Holmes, MD, medical/hematology oncologist at Texas Oncology in Houston.

Case 1

How should a patient with triple-negative metastatic breast cancer be treated if she received adriamycin and cyclophosphamide with Taxol (ACT) in the adjuvant setting a year ago?

The panel noted that patients like this one are often difficult to treat because patients with triple-negative breast cancer who recur quickly like this are often refractory to ACT (doxorubicin/cyclophosphamide/paclitaxel), which means that they are likely to be refractory to several other chemotherapy agents.

However, the panelists were quick to note that this does not mean that all chemotherapy agents will be ineffective in treating this patient. The panel referred to a study in which gemcitabine/carboplatin with iniparib was used to treat patients with triple-negative breast cancer. Patients who were given gemcitabine/carboplatin had approximately a 30% response rate with about 6 months of progression-free survival and approximately 1 year overall survival.

Based on the experience of the panel, patients with triple-negative breast cancer tend not to benefit from platinum-based regimens. In this particular case, the panelists felt that eribulin would be another reasonable treatment option. However, the data on how patients respond to eribulin is not very robust because many of the patients in the studies have been heavily pretreated by the time they are enrolled in the trials.

Bevacizumab might also be an option for this patient, but the panel noted that this would depend on whether a triple-negative breast cancer patient has an amplification of vascular endothelial growth factor A (VEGF-A), which tends to be overexpressed in many triple-negative cases.

The panel pointed to promising developments on the horizon that might benefit this particular patient. For example, by the end of 2011, the Human Genome Atlas Project is expected to be completed, and it will give oncologists a better understanding of the key mutations and amplicons indicated in breast cancer. In addition, future studies of novel clinical trials might be exactly what this patient and others like her need.

The panel concluded that somebody who is fairly refractory to ACT is highly unlikely to get a very durable benefit from more cytotoxic therapy.

Case 2

A 37-year-old woman has stage III invasive ductal breast cancer. She is estrogen receptor—positive (ER ) and human epidermal growth factor receptor–positive (HER ), but her progesterone receptor status is unknown. She’s had a bilateral mastectomy performed. She has received ACT for chemotherapy and is continuing on trastuzumab. She has not yet started to take tamoxifen because she is hoping to get pregnant. She has declined a luteinizing hormone-releasing hormone (LHRH) agonist due to her concerns about the side effects. She wants a natural pregnancy and wants to time it appropriately and inline with her treatment. She has 3 embryos available, but no surrogate to carry the embryos. She is a BRCA wild- type, she is not a mutation carrier, and she has resumed menstruation.

As her oncologist, would you encourage gonadotropin-releasing hormone (GnRH) agonist or oophorectomy with tamoxifen? Would you discourage her from trying to achieve a natural pregnancy or carrying the embryo? Is there enough time for an ideal pregnancy? If this patient delays tamoxifen for the sake of the pregnancy, is there a role for tamoxifen after she has given birth?

The panel acknowledged that a patient wanting to become pregnant during a course of treatment for breast cancer is not uncommon among younger women. However, in this particular case there is also the issue of whether the patient is triple-positive, since her progesterone receptor (PR) status is unknown. If she is triple-positive, it is important to know which mutation is dominant because it may end up guiding her treatment options.

The panel discussed its experience with a similar case of a 29-year-old patient who had locally advanced triple-positive disease and who also wanted to become pregnant. The patient was treated with FEC 75 (5-fluorouracil, epirubicin, and cyclophosphamide) with trastuzumab.

The patient’s cancer was highly proliferative. After 2 cycles of adjuvant chemotherapy, the patient’s cancer was not growing, but it was not responding either. A decision was made to add endocrine therapy via an LHRH agonist starting with cycle 3. By the time the patient came in for cycle 4, the palpable axillary adenopathy was gone and the tumor had shrunk by 50%. Based on past experience that demonstrated the value of endocrine therapy in patients with triple-positive breast cancer, the panel expressed concern as to why this young woman is declining adjuvant endocrine therapy at this time.

The panel did not see a problem with starting tamoxifen therapy to see if the patient responded, and then taking her off the therapy while she attempts to get pregnant, assuming that the patient would resume the tamoxifen therapy soon after the birth of the child.

“When patients have serious breast cancer like this young woman with stage III disease, I think that a few years of tamoxifen LHRH agonist is an appropriate treatment,” said O’Shaughnessy. “We know that 5 years of tamoxifen is better than 2 from the Oxford Overview. We don’t know that 3 is better than 2, but since 5 is better than 2, if I get patients on the therapy for 2 to 3 years, I’m usually pretty happy with that.”

In the end, the panel stressed the importance of having a close relationship with the patient so that decisions are made together.

“If you partner with the patient to make decisions about treatment, the patient will feel more empowered and focused on the big picture, which will put her in a better position to deal with the side effects of the LHRH-agonist therapy,” said O’Shaughnessy.

Case 3

A 43-year-old black woman has a 6.5 cm ductal carcinoma in situ (DCIS) and multifocal, microinvasive disease. A total mastectomy and sentinel lymph node dissection are performed. One of the sentinel lymph nodes is immunohistochemistry (IHC) cytokeratin—positive. The IHC analysis revealed the following results: I , NOI , ER is 18% positive, PR is 17% positive, and Ki-67 is 45% positive.

Should the patient receive adjuvant treatment?

The panel began its discussion of this case by pointing out that there was no right or wrong answer to this challenging case.

Based on data discussed in previous sessions of the conference, studies have shown that patients with cytokeratin-positive cells in lymph nodes did have a slightly worse prognosis than patients who were node-negative. The DCIS diagnosis is also a concern because of the large area affecting the breast, increasing the chance that something could be missed.

“[Even] if you weren’t missing something, multifocal microinvasive disease has a much more aggressive biology,” said O’Shaughnessy.

Despite the higher probability of a poorer diagnosis, the panel said it would treat the patient with adjuvant therapy, and start her on ACT therapy.

In addition to ACT, the panel said it would also recommend tamoxifen. However, there were a number of lingering concerns to this approach. The panel would look for lymphovascular invasion (LVI), where cancer cells invade blood vessels or the lymphatic system. While there would likely be no role for radiation therapy if there was no sign of LVI, if there was any question about whether LVI was an issue, the panel’s recommendation would be to consult with a radiation oncologist as quickly as possible.

Case 4

A 61-year-old woman presented with stage IV ER /HER breast cancer. She received paclitaxel/trastuzumab. She had a complete response and has been in complete remission for 2 years. The patient has now developed central nervous system (CNS) metastasis. She has 2 brain lesions, but there is no evidence of systemic disease. There is no evidence of disease outside of her brain.

Should the patient receive some sort of radiation to the brain, or are there other treatment options for her?

In this case, the panel noted similarities to several patients who have gone through the same experience in their clinics.

One of the panelists (Rugo) said her clinic uses stereotactic radiosurgery in this setting, either Gamma Knife or CyberKnife, depending on the location of the lesions. Rugo would also add lapatinib to the patient’s existing trastuzumab and hormone therapy. At Rugo’s clinic, they occasionally add another stereotactic radiosurgery.

Rugo described another patient who did not have CNS disease but had disease outside the brain. “I gave the patient 6 different combinations.... [We had] exhausted all options,” Rugo explained. “The patient was only 25 years old with 2 small children. I gave her one last combination, trastuzumab and bevacizumab. The patient has had 6 months of complete disease control without any toxicity.”

Another panelist (Holmes) indicated that she has had a number of similar patients who have been handled in different ways. For example, one patient who is in remission from liver and bone metastases is being treated with focal radiation therapy.

“If the patient has either systemic disease that’s not well-controlled or if the brain disease recurs after whole-brain radiotherapy, I put the patient on capecitabine. Then I wait. That’s an interesting thing because I don’t think we really know when to go in early versus waiting, but I take the waiting approach.”

Holmes described another patient who had stage IV disease and lymphedema, which was successfully managed for several months. But after 2 years of treatment, the lymphedema returned and is the only site of disease. The patient is now on trastuzumab/lapatinib.

The moderator (O’Shaughnessy) concurred with Rugo and Holmes, yet indicated that she would do stereotactic surgery as opposed to whole-brain radiation therapy, and would continue trastuzumab to keep the disease from spreading. As far as endocrine therapy, O’Shaughnessy said she would definitely add lapatinib, but she was undecided about adding capecitabine to the therapy regimen. However, she concluded that she would consider adding capecitabine to the patient’s therapy in an attempt to achieve maximum control.

Participation from the attendees contributed to the complexity and intricacy of these already challenging cases. “We’re all informed by the anecdotal successes that we’ve had in our practice,” said Holmes.

Sharing these personal treatment decisions in an open forum like the International Congress on the Future of Breast Cancer meeting provides opportunities for continued learning, and may ultimately lead to improved patient outcomes and quality of care.