19 April 2020

The US Food and Drug Administration (FDA) has recently approved a new treatment for patients with metastatic breast cancer. Tucatinib (Tukysa) was approved for use in combination with 2 other agents, trastuzumab (Herceptin) and capecitabine (Xeloda) in patients with unresectable (too advanced to remove with surgery) or metastatic (spread to other areas of the body, such as bone, liver, lungs or brain) Her2/neu over-expressed breast cancer (Her2+). Tucatinib is approved for patients who have already been treated with one or more anti-Her2/neu treatments.

Tucatinib is a an oral (pill) medication known as a tyrosine kinase inhibitor. Results of the Her2CLIMB trial were presented in December at the San Antonio Breast Cancer Symposium. The study enrolled 612 patients with metastatic or unresectable Her2+ breast cancer who had received at least one other Her2+ targeted agent but were experiencing progression of disease. Unique to this study was that almost half of the participants had metastases to the brain – often these patients are excluded from clinical trials.

Some of the key findings were that in patients who received tucatinib with trastuzuab and capecitabine versus those who received trastuzumab and capecitabine alone:

  • Median progression free survival was 7.8 months versus 5.6 moths
  • Median progression free survival for patients with baseline brain metastases was 7.6 versus 5.4 months
  • Median overall survival was 21.9 versus 17.4 months
  • Confirmed objective response rate was 40.6% versus 22.8%

Serious adverse reactions occurred in 26% of patients and 6% of patients had to stop treatment due to adverse reactions. The most common side effects were diarrhea, hand-foot syndrome, nausea, fatigue, liver toxicity, mouth sores, decreased appetite, abdominal pain, headache, anemia and rash.

The approval of tucatinib provides another option for patients with aggressive breast cancer, including those who have brain metastases. However, as previously discussed, this study is a reminder of how far we have to go to achieve a reliable and long-lasting treatment response in patients with metastatic breast cancer.

Additional Information:

15 March 2020

Ductal carcinoma in-situ, also known as DCIS or stage 0 breast cancer, is traditionally treated with surgical excision (lumpectomy or mastectomy). Treatment may also include radiation therapy, as well as endocrine therapy (tamoxifen or an aromatase inhibitor) if the disease is estrogen receptor positive (ER+).

For invasive cancer, we sometimes take a neoadjuvant approach, treating with chemotherapy or endocrine therapy prior to surgery. This has the advantage of confirming that the tumor will actually respond to treatment. In addition, in cases where the tumor does not completely resolve with treatment (based on pathology assessment of the tissue that is removed), additional chemotherapy or targeted treatments may be recommended.

We have not traditionally used a neoadjuvant approach for DCIS. While invasive cancers may shrink in response to treatment, it is unclear if that reliably happens with DCIS. A study recently published used letrozole (Femara – an aromatase inhibitor) in patients with ER+ DCIS. Patients were treated for 6 months, had MRIs at baseline, 3 and 6 months, and then underwent surgery. The size of abnormality on MRI (which often, but not always correlates with the amount of disease) was measured, and ER, PR (progesterone receptor) and Ki67 (a measure of cellular proliferative activity) was assessed on the pre-treatment needle biopsy and on the surgical specimen. 79 patients were enrolled, 70 completed 6 months of letrozole, and MRI data for all 3 time points was available for 67 patients.

The study found that:

  • Median volume of disease as measured by MRI declined by 0.8cm 
  • ER and PR H-scores decreased by a median of 15 and 85 points, respectively
  • Ki67 decreased by a median of 6.3%

Of the 59 patients who underwent surgery, findings included:

  • Persistence of residual disease in 50 patients (85%)
  • Invasive cancer in 6 patients (10%)
  • No residual DCIS and no invasive cancer found in 9 patients (15%)

As mentioned above, the finding of residual disease is not unexpected. DCIS does not often resolve after neoadjuvant therapy, and endocrine therapy works very slowly. In addition, several patients were found to have invasive cancer – the authors suspect that most likely this was not picked up on the initial biopsy as we know the “upstaging” rate for DCIS at surgery can approach 25%. However, despite these limitations, the finding of decreased volume of disease by MRI and changes in biomarkers (ER, PR and Ki67) indicate treatment response and suggest that extended neoadjuvant endocrine therapy may eventually play a role in the treatment of ER+ DCIS and may possible replace surgery in selected patients. This was a relatively small Phase II trial, so more study certainly is needed. 

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

25 December 2019

Two studies recently presented at the recent San Antonio Breast Cancer Symposium focused on a subtype of breast cancer known as Her2/neu over-expressed, which include up to 20% of breast cancers. In these tumors, the gene that codes for the Her2 protein receptor has more than the usual number of copies. These tumors tend to have more aggressive growth patterns and up until the development of targeted antibody therapy, prognosis was very poor. 

Targeted antibody therapy including trastuzumab (Herceptin) and pertuzumab (Perjeta) is now standard of care for Her2 breast cancers, even in the setting of early-stage disease. Trastuzumab emtansine (Kadcyla, T-DM1) is an antibody-drug conjugate (ADC, a combination of the antibody and a chemotherapy agent) and is most commonly used in patients with metastatic disease. Unfortunately, not all Her2 tumors respond to therapy, and some tumors that initially respond can mutate and become resistant to therapy. Brain metastases can occur in up to 50% of patients with metastatic Her2 breast cancer, and can be challenging to treat as medications may not be able to pass through the blood-brain barrier to get to the cancer cells. 

Trastuzumab deruxtecan (DS-8201, Enhertu) is an ADC and results of a phase 2 study (DESTINY-Breast01*) were presented. This study included 184 patients with metastatic Her2 breast cancer, who were experiencing disease progression after receiving 2 or more different anti-Her2 treatment protocols (including trastuzumab emtansine, median 6 prior therapies, range 2-27). This was an “open label” study and patients were not randomized. Median follow up was 11 months and findings included:

  • Median treatment duration was 10 months
  • Overall response rate was 60.3% (at least 2 follow up scans, 6 weeks apart)
  • 11 patients (6%) experienced a complete response (apparent resolution of disease)
  • 101 patients (55%) experienced a partial response
  • Median duration of response to treatment was 14.8 months
  • In patients with brain metastases (24 patients), median progression-free survival (PFS, time to disease advancement) was 18 months
  • Adverse events (AE) occurred in all but one patient. The most common AE were nausea, hair loss, vomiting, constipation and neutropenia (low white blood cell count) 
  • 57% of patients experienced more serious (≥ grade 3) AE
  • 28.8% of patients stopped treatment due to disease progression
  • 15.2% of patients stopped treatment due to AE
  • One of the more serious complications, interstitial lung disease (ILD), was reported in 25 patients and 4 patients died due to ILD-related causes

Shortly after the study was presented, the drug received accelerated FDA approval for patients with unresectable (not able to be removed with surgery) or metastatic Her2 breast cancer who have experienced disease progression after treatment with 2 or more targeted agents. The approval is accompanied by a warning due to risks of ILD as well as embryo-fetal toxicity. 

ASCO Post coverage of trastuzumab deruxtecan

The other study involved Tucatinib, which is a tyrosine kinase inhibitor, administered in pill form. The Her2CLIMB trial* was a Phase 3 study that included patients with Her2 metastatic breast cancer who previously received treatment with trastuzumab, pertuzumab, and trastuzumab emtansine. Patients with and without brain metastases, including untreated brain metastases, were included. Patients in this trial received either tucatinib or placebo, in combination with trastuzumab and capecitabine (Xeloda – an oral form of chemotherapy).

The study included 612 patients. 410 received tucatinib-trastuzumab-capecitabine (T-C) and 202 received placebo-trastuzumab-capecitabine (P-C). 48% of patients in the T-C group and 46% of patients in the P-C group had brain metastases at enrollment. Median follow up was 14 months and findings included:

  • At one year, PFS was 33% in the T-C group and 12% in the P-C group
  • At one year, median duration of PFS was 7.8 months in the patients who received T-C and 5.6 months in the patients who received P-C
  • Overall survival (OS) at 2 years was 45% in the patients receiving T-C and 27% in those who received P-C
  • Median OS was 21.9 months in the patients receiving T-C and 17.4 moths in the patients who received P-C
  • Among patients with brain metastases, estimated PFS at one year was 24.9% in the T-C group and 0% in the P-C group
  • Among patients with brain metastases, median duration of PFS was 7.6 months in the T-C group and 5.4 months in the P-C group
  • The most common adverse effects in the patients in the T-C group were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting
  • 23 (5.7%) patients in the T-C arm and 6 (3.0%) patients in the P-C arm discontinued therapy due to side effects
  • Of the 215 deaths that occurred during the study, the most common reason was disease progression. Adverse events were the cause of death in 6 (1.5%) of patients in the T-C group and 5 (2.5%) in the P-C group

ASCO Post coverage of tucatinib

While these 2 studies demonstrate the progress that has been made in treating an aggressive form of breast cancer, they also serve as a sobering reminder of the work that remains. The hope with targeted therapy is that cancer cells will be killed with minimal toxicity to other cells or the person – we are not quite there yet. In addition, while the improvements in progression free and overall survival is encouraging, we are not yet able to ensure long-term survival for patients with metastatic Her2 breast cancer. If you donate to breast cancer research organizations, please consider this when deciding which groups to support.

*If you are not able to access the full studies and would like a copy, please email me: contact at drattai dot com

21 November 2019

Following lumpectomy, radiation therapy to the whole breast is a standard part of breast conserving therapy (BCT). The use of radiation therapy after lumpectomy has been shown to reduce local (in the breast) recurrence rates. Radiation therapy can be administered in several ways, but most commonly, the whole breast is treated (whole breast irradiation, WBI). Treatments are usually administered 5 days per week, over the course of 3-6 weeks, depending on the specific protocol that is followed.

One of the disadvantages to this approach is that if there is a recurrence of cancer in the breast after treatment, mastectomy is usually recommended due to concerns about wound healing problems as well as toxicity from administering radiation a second time. However, newer techniques and the ability to target the lumpectomy site more precisely may give some women who develop a recurrence after initial BCT another option.

The results of the NRG Oncology / RTOG 1014 study were recently published in JAMA Oncology*. Patients who initially underwent BCT and developed a recurrence greater than one year from initial treatment that was ≤3cm and was unifocal (one area of disease) were eligible to participate. All patients underwent surgical removal of the recurrence with clear margins. Following surgery, external beam radiation, focused to the lumpectomy site, was administered. The study enrolled patients from 2010 – 2013 and follow up through 2018 was included in this publication. Median follow up was 5.5 years.

65 patients were enrolled, and 58 were evaluable. Of those, 91% had tumors ≤2cm (median tumor size 1.0cm) and none had suspicious lymph nodes. 23 (40%) had DCIS and 35 (60%) had invasive cancer. 44 (76%) had ER+ tumors. Of these 58 patients, 4 developed yet another recurrence, all non-invasive, for a 5-year local recurrence rate of 5%. A total of 7 patients underwent mastectomy – 4 with recurrent disease, 2 due to wound healing complications, and one in a patient who developed cancer in the other breast and subsequently underwent a bilateral mastectomy. Both metastasis-free survival and overall survival was 95%. Toxicities were mostly graded as minor.

The conclusion of the authors was that external beam partial breast re-irradiation is “an effective alternative to mastectomy” in select patients who develop a local recurrence after BCT. Drs. Cook and DiNome, in an accompanying editorial*, note some of the limitations of the study: patients were older, mostly white, with relatively small low-grade tumors. Therefore, the results may not be applied to all patients. However, they agree that for selected patients who are motivated to avoid mastectomy in the setting of recurrence after BCT, partial breast re-irradiation is a reasonable option to consider.

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

3 September 2019

Last week, the US Food and Drug Administration (FDA) issued draft guidelines for industry, which encourage the inclusion of male breast cancer patients in clinical trials that evaluate breast cancer therapies. The guidelines note that “eligibility criteria for clinical trials of breast cancer drugs should allow for inclusion of both males and females” and that “scientific rationale should be included in the protocol when proposing to exclude males from breast cancer trials.” There is a 60-day open comment period on the guideline.

In the US, approximately 2600 men are diagnosed with breast cancer each year, approximately 1% of all new breast cancer cases. Men tend to be diagnosed at more advanced stages compared with women, and there are about 500 male breast cancer related deaths in the US annually. Breast cancer in men is usually treated in a similar manner as in women. However, because men are typically not included in breast cancer clinical trials, it is not known if this is an optimal approach. One of the primary reasons that men are excluded from breast cancer clinical trials is that the disease is uncommon – setting up a vicious cycle where little progress is made. The statement noted that “FDA does not intend to consider low expected accrual rates of male patients with breast cancer to be a sufficient scientific rationale for excluding them from a clinical trial.”

This is most certainly a welcome step towards improving the understanding and treatment of male breast cancer.

8 July 2019

Patients who have been diagnosed with atypical ductal hyperplasia (ADH) and lobular carcinoma in-situ (LCIS) have a much higher risk of developing breast cancer compared with the average population, usually well over the “high risk” threshold of 20%. Tamoxifen is recommended for these patients to reduce help reduce subsequent breast cancer risk, but a relatively low percentage of patients actually take it, often due to concerns about side effects. 

In December 2018, the TAM-01 study was presented at the San Antonio Breast Cancer Symposium. This study used a reduced dose (5 mg instead of the usual 20 mg daily) of tamoxifen in women who had ADH, LCIS or ductal carcinoma in situ (DCIS) to see if a lower than standard dose could effectively reduce breast cancer risk.

The full manuscript* has recently been published. 500 women with a history of ADH, LCIS or DCIS were randomized to receive 3 years of either low dose tamoxifen or placebo. The study was performed in Italy. Mean patient age was 54, and 55% of the patients were post-menopausal. 20% had ADH, 11% had LCIS, and 69% had DCIS. 

With a median follow up of 5.1 years, there were 14 cancers (invasive or DCIS) in the tamoxifen group and 28 in the placebo group (11.6 versus 23.9 per 1000 person-years). Tamoxifen decreased the number of contralateral (opposite side) events by 75% but numbers were low (3 versus 12). Daily hot flashes in patients receiving tamoxifen were more frequent (2 versus 1.5 per day) than in patients receiving placebo. There were no differences in patient-reported hot flash score (combination of hot flash frequency and intensity), vaginal dryness, pain during sexual intercourse, or joint / muscle pains between the 2 groups. There were fewer serious adverse events (blood clot, pulmonary embolus, uterine cancer) in the patients receiving tamoxifen versus placebo (12 versus 16). 65% of patients in the tamoxifen arm and 61% in the placebo arm took ≥85% of pills for the first 2 ½ years of the study. The authors concluded that low dose tamoxifen for 3 years can reduce the risk of invasive or non-invasive breast cancer, with similar side effects to placebo. 

It is important to stress that this is one study, with a relatively small number of patients – 195 of the 253 in the tamoxifen arm completed the study. An important finding is that the authors found risk-reducing effects after only 3 years of therapy. However, current guidelines do still recommend standard (20mg) tamoxifen for 5 years for high risk patients as well as those with a history of estrogen-receptor positive (ER+) DCIS. There is no data on the use of low dose tamoxifen for invasive breast cancer treatment. However, for patients who are reluctant to take the full dose of tamoxifen, or who have significant side effects, it may be reasonable to consider a reduced dose – taking into account the patient’s individual risk, side effects of the standard 20mg dose, and the limitations of this study.

*Journal of Clinical Oncology Editorial: Will a low-dose option improve uptake of tamoxifen for breast cancer risk reduction?

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

5 July 2019

We tend to think of most cancers as a single cell line, or clone – one normal cell develops a mutation, and that abnormal cell continues to divide. However, many tumors exhibit what is termed “heterogeneity” – meaning they are composed of cells with different genetic makeups. These cells can have different behaviors, growth patterns and response to treatment.

A study recently published in the Annals of Surgical Oncology looked at the association between tumor heterogeneity and immune cells. They found that tumors with high heterogeneity (more diverse cell population) were associated with worse overall survival. They also found that these tumors were associated with lower levels of anti-tumor T-cells (an immune system cell) and “immune checkpoint molecules”, and had a higher percentage of immunosuppressive T-cells. Their finding was noted primarily in estrogen-receptor positive (ER+) breast cancers.

Testing for different cell populations within a tumor is not routinely performed at this point in time. In addition, the authors noted that it is up for debate (and further research) which comes first – do the diverse tumor cell populations attract immune cells, or do the immune cells act to control tumor cell diversity. They noted that additional work is needed to better understand the changes that influence tumor cell heterogeneity and to develop methods to prevent it from occurring. This is just one of the reasons why a “cure” for cancer is not that simple. Cancer – even a single tumor in one patient – is not just one disease.

30 June 2019

Note – if you would like a copy of the studies discussed below but are not able to access them from the journal website, please email me: contact at drattai dot com

In a study recently published in the Annals of Surgical Oncology, Bateni et al used the National Cancer Database to assess outcomes in patients with male breast cancer based on surgical therapy. The authors found improved 10-year survival in patients who underwent breast conserving therapy (BCT) which they defined as partial mastectomy (also called lumpectomy) plus radiation therapy.

Male breast cancer makes up about 1% of all new breast cancer diagnoses; approximately 2500 men are diagnosed in the US each year. Treatment guidelines for male breast cancer are similar to those for post-menopausal women despite growing evidence that breast cancer in men is a biologically different disease versus that in women. One of the challenges for clinical trials is the relatively small numbers of male breast cancer patients diagnosed each year. However, many clinical trials have not included men. 

A total of 8445 patients with stage I and II breast cancer, treated between 2004-2014, were included for analysis. 61% underwent mastectomy, and 18% underwent BCT. 12% had mastectomy with radiation, and 8% had partial mastectomy without radiation. Median follow up was 52 months. At 10 years, overall survival was as follows:

  • 74% BCT
  • 58% mastectomy
  • 56% mastectomy with radiation
  • 56% partial mastectomy without radiation

The image below is Figure IA from the manuscript, which show the “crude” overall survival for male breast cancer patients depending on surgical therapy.

Evaluating patients who had breast conservation with or without radiation, the authors noted that patients who were older, had higher tumor stage, higher cellular grade, and triple negative histology had poorer overall survival rates. They noted that there were differences in patient age, co-morbidities (other medical conditions), margin status and chemotherapy use for patients who underwent BCT versus partial mastectomy alone. However, after accounting for these differences, survival rates still favored BCT, suggesting that radiation therapy is an important component of improved outcomes. 

Limitations of the study noted by the authors include the retrospective nature, and the inability to understand some of the factors that influenced the decision for mastectomy versus breast conservation. Her2/neu status was not uniformly reported in the NCDB until 2010, so almost half of the patients in this study did not have this information. They also noted a larger percentage (4.9 vs 1.4%) of patients in the BCT group had triple negative breast cancer, which might explain why more of these patients were also treated with chemotherapy. It is also not clear how much of an influence the use of chemotherapy and endocrine therapy had in terms of the survival rates that were noted.

In a separate article, De La Cruz et al performed a systematic literature review of the studies evaluating breast conservation in men (excluding the Bateni et al study discussed above). The authors found 8 publications meeting their criteria. Among these studies, there were 859 patients who underwent breast conservation, 14.7% of all male breast cancer surgeries in the combined papers. Reporting on the “weighted average”, local recurrence (cancer returning in the breast) was 9.9%, disease-free survival was 85.6% and 5 year survival was 84.4%. As with the retrospective database analysis, there are limitations to this type of literature review – studies may use the same data points for inclusion, including use of radiation therapy, chemotherapy, and margin status. There may be significant differences in the patient populations in the various studies reviewed. As in the Bateni et al paper, there may be multiple unknown factors that influenced a decision for surgery type.

Men tend to present with larger tumors, especially relative to breast size, so often mastectomy is recommended. However, the authors of both papers were of the opinion that breast conservation is oncologically safe and a very reasonable option for men with early stage breast cancer, if they desire. Bateni et al stressed the importance of radiation therapy if breast conservation is utilized. Both papers highlight the importance of clinical trials for male breast cancer, so that treatment recommendations can be based on the best available evidence.

Additional information on Male Breast Cancer:

13 May 2019

Note – the survey closed on July 7th 2019. Thank you to all who participated and shared, and we will be sure to post the results when they are available!

Approximately 25-30% of patients with breast cancer who are prescribed endocrine therapy do not complete the full course of treatment, and some patients never start. Side effects of endocrine therapy are well documented but there is very little literature on the role of the medical team in helping patients manage treatment-related side effects. 

This survey is being conducted for research purposes. It is a UCLA research survey, open to women and men with a history of breast cancer who have been treated with or who have received a recommendation for endocrine therapy. 

This survey is voluntary and is completely anonymous – no identifying information, including internet protocol (IP) addresses, will be collected. The survey should take approximately 15 minutes to complete. We value your time and your opinions. 

For questions regarding this study, you may contact principal investigator Dr. Deanna Attai By phone: (818) 333-2555; by email: dattai@mednet.ucla.edu; or by mail: 191 S. Buena Vista #415, Burbank, CA 91505

UCLA Office of the Human Research Protection Program (OHRPP):
If you have questions about your rights as a research subject, or if you have concerns or suggestions and you want to talk to someone other than the researchers, you may contact the UCLA OHRPP  By phone: (310) 206-2040; by email: participants@research.ucla.edu; or by mail: Box 951406, Los Angeles, CA  90095-1406

Research Survey Link

6 March 2019

The American Society of Breast Surgeons (ASBrS) held their annual meeting in Dallas last week. This meeting usually draws about 1500 breast surgeons (just under half the ASBrS membership) from around the world, for several days of pre-meeting courses, didactic sessions, and research presentations. In addition to the science, the meeting provides opportunities for breast surgeons in all types of practice settings and at all levels of training and practice to network and learn from each other. 

The following covers some highlights from the general session. 

The meeting started off with the Critical Issues in Breast Cancer Forum: Changing Paradigms for Breast Cancer Surgery. Dr. Cary Kaufman presented an update on current clinical trials for cryoablation for breast cancer. Cryoablation is a technique that freezes the tumor, using a small probe placed into the tumor (similar to a needle biopsy) under local anesthesia. There are several types of ablative therapy including laser, radiofrequency, high-frequency ultrasound, and cryoablation. Because cold is a natural anesthetic agent, patients undergoing cryoablation do not need any sedation, and the procedure is performed while they are awake. 

Cryoablation was initially tried with benign tumors (fibroadenomas). In many cases, the fibroadenoma reabsorbed, leaving no mass and only a tiny (3 millimeter) scar. Multiple studies have looked at the use of cryoablation for breast cancer, and most have restricted therapy to patients with small (1.5 cm or smaller) estrogen receptor positive, Her2/neu negative tumors. I participated in a national multi-center trial, the ACOSOG / ALLIANCE Z1072 trial, which was published in 2016 and demonstrated that cryoablation was successful in the majority of these patients. All patients in the ACOSOG / ALLIANCE Z1072 study underwent surgery within one month of the ablation, so that the tumor site could be removed and evaluated. Several subsequent studies have looked at cryoablation for breast cancer without surgery. The longest follow up was from Dr. Fukuma in Japan. After 12 years of follow up, he reported 3 local (in-breast) recurrences in 304 patients. Combining 3 published trials, Dr. Kaufman noted that local recurrence rates range from 0.98 – 1.4%, and he concluded that this is extremely promising technology. He also noted that cryoablation of breast cancer appears to have an immunologic benefit – when the tumor cell membranes are disrupted by the extreme cold, the patient is exposed to tumor antigens, which may prompt antibody formation. It is very premature to determine if this immunologic effect will help reduce recurrence rates.

Dr. William Small presented updates on 3 clinical trials of intraoperative radiation therapy (IORT). An advantage of IORT is that it is delivered at the time of lumpectomy, in the operating room, as a one-time treatment. A disadvantage is that status of the lumpectomy specimen margin and lymph nodes are not known at that time. If it is found on final pathology that there are positive margins, external beam radiation is recommended, and at least one trial noted that approximately 30% of patients who received IORT required additional whole breast radiation. Most studies of IORT have been limited to “low risk” lesions – small, low grade invasive cancers in older women. He discussed that a criticism of these studies is that some of these women may not have needed radiation therapy at all. Dr. Small noted that local recurrence rates are slightly higher (3.3 versus 1.3%) but that statistically, IORT is considered “non-inferior” to whole breast irradiation. He noted that seroma (fluid accumulation) is more common in patients who undergo IORT.  He concluded by stating that there is an “acceptable” toxicity, with non-inferior local recurrence. However, as there is relatively short follow up available in low risk patients, he questioned the applicability of this procedure to a broader patient population. A US registry is planned.

Dr. Antonio Toesca presented the results of his study of 100 patients who underwent robotic nipple sparing mastectomy (NSM) and implant reconstruction, and showed a fascinating video which highlighted the precise and meticulous dissection, along with improved visualization, compared to a standard surgical procedure. The average incision size was a little over 1 inch, and the specimen was removed intact (in one piece). The procedure averaged 1 hour and 18 minutes longer than their standard for a nipple sparing mastectomy and implant reconstruction (3 hours, 36 minutes for the robotic procedure. Patients who underwent the robotic procedure were less likely to have axillary web syndrome and reported Improved physical, psychological and sexual well-being. 

Why could performance of NSM using robotic technology become important? Dr. Tina Hieken presented the results of her study (abstract 580759, page 31) showing that as experience with the procedure has grown, indications are expanding and patients who previously were not candidates for the procedure are now being considered. A NSM is a technically challenging procedure, and it takes a toll on the neck and back of a surgeon. A 2017 study published in JAMA Surgery noted a high incidence of work-related musculoskeletal disorders among surgeons and interventionists. Dr. Katherine Kopkash presented her research (abstract 51837, page 52) using intraoperative electromyography (EMG) on the surgeon to assess muscle strain during NSM. Of course, oncologic safety is the primary concern, and more study on the long-term outcomes (as well as costs) of robotic procedures is required. 

The next session was Emerging Strategies in Breast Cancer Care, which focused on “de-escalation” of surgical therapy. Dr. Anna Weiss provided an update of clinical trials evaluating active surveillance for low-risk ductal carcinoma in-situ (DCIS): COMET, LORD and LORIS. Approximately 60,000 cases of DCIS are diagnosed annually. Patients undergoing active surveillance do not have surgery, some are treated with endocrine therapy, and all undergo regular monitoring. This is a accepted option in select cases of prostate cancer, and Dr. Weiss noted that there is no difference in overall survival in patients with low-grade DCIS who do not undergo treatment. The LORD and LORIS trials are open in the UK and the COMET study is open in the US. (Additional perspective)

Dr. Henry Kuerer presented his research on the percutaneous management of breast cancer in the setting of a pathology complete response (pCR) following neoaduvant (before surgery) chemotherapy. He noted that for survival and recurrence matter most, but side effects and complications are significant concerns for both patients and physicians. I’ve recently covered details of his research on this blog

Some of the twitter conversation related to this talk included patients who noted that they would rather undergo surgery than chemotherapy. It is important to note that the patients involved in this study are those who were going to be treated with chemotherapy regardless of surgical therapy because they have triple negative or Her2/neu positive breast cancer. In these patients, systemic (whole-body) therapy is necessary due to the higher likelihood of metastatic disease. Surgical therapy in these patients, especially the “exceptional responders”, may not improve outcomes, but of course more study is needed. Surgery remains the standard of care for breast cancer therapy.

Dr. Judy Boughey discussed several cooperative group trials evaluating management of the axillary (underarm) lymph nodes, and these studies are also focusing on how we can safely de-escalate axillary surgical therapy after neoadjuvant chemotherapy. This is an area that is rapidly evolving with expansion of the criteria for a less aggressive approach to the axilla.

In a session on Evidence-Based Prevention and Management of Surgical Complications, Dr. Suzanne Klimberg presented on chronic post-mastectomy seroma. A seroma is a fluid collection – fluid normally accumulates after mastectomy which is why drainage tubes are left in place. Normally, drains can be removed after 7-14 days, but about 30% of patients will develop prolonged drainage. This is a frustrating problem for patients and physicians as the persistent fluid can be uncomfortable, may increase the risk of infection, and may delay the start of planned chemotherapy or radiation. She noted that a surgical technique to close the tissue known as “quilting” can reduce the rate of chronic seroma, but that it results in excessive skin dimpling and has a significant impact on the cosmetic results. She stated that additional drainage tubes, various “sealant” agents and compression (such as wearing an ace wrap) are not effective. The area may be sclerosed (scarred) by instilling talc or antibiotics, and in some cases, re-operation to remove the inflamed tissue is indicated. Otherwise she recommended patience and repeat aspirations. She noted that there are no ways to successfully prevent seromas from forming.

Dr. Amal Khoury presented on chronic post-mastectomy pain, and noted that persistent pain occurs in 25-60% of patients undergoing any type of breast surgery. It is thought that this chronic and at times severe pain is due to damage to and neuroma formation of the cutaneous (skin) branches of nerves that run along the 4thand 5thribs, which are roughly at the inframammary fold (bra line below the breast). These cutaneous nerve branches are often not visible at the time of surgery. She noted that the pain syndrome it is often not recognized, and when recognized it is often not treated effectively. She stated that injections with a combination of long-acting local anesthetic and steroid (in a very small dose) at the trigger points is more effective than taking pain or other medications, and in their study at UCSF, 91% of patients required only one injection for lasting relief.

The next session was Practical Considerations for Systemic Treatment. Dr. Judy Boughey reviewed the I-SPY2 clinical trials, which utilize an innovative “adaptive randomization” approach in patients who are undergoing neoadjuvant chemotherapy for triple negative, Her2/neu positive, or other high risk breast cancers. pCR rates are assessed, and drugs that are successful move up higher in the randomization algorithm. This study and its flexible randomization protocol have accelerated the use of some novel agents. Patient reported outcomes assessing quality of life, fear of recurrence, symptoms and side effects are being assessed. If drug response rates are similar, the “winner” may be the one associated with fewer side effects. Dr. Barry Rosen discussed specific strategies to identify the previously involved axillary lymph nodes when chemotherapy is performed prior to surgery. Dr. Elizabeth Mittendorf presented on breast cancer immunotherapy and surgical implications of these treatments. She noted that one agent, atezolizumab, is currently approved for use in patients with metastatic triple negative breast cancer. She noted that there are concerns about wound healing complications with these agents but unfortunately the clinical trials did not specifically assess for this. In addition, she noted that some immunotherapy agents are associated with development of adrenal insufficiency – this complication has only been reported in a small percentage of patients, but it is an important consideration in any patient who is going to have surgery.

A session was held on breast imaging. Dr. Molly Sebastian presented on the impact of breast density on breast cancer risk, noting that it is more difficult to screen patients with dense breasts, and that these patients are also at increased risk for developing breast cancer. The associated breast cancer risk increases with the level of density. Approximately 50% of women in US are considered to have dense breast by mammogram, and she cited a 2010 study that found that 30% of breast cancers could be linked to highly dense breast tissue. Contributors to increased density include younger age, use of hormone replacement therapy, race (Asian), diet (Western), alcohol use, and hereditary factors. She did stress that the presence of a germline genetic mutation (such as BRCA 1/2) conveys a much higher level of risk (regardless of density) than breast density itself. 

Dr. Brigid Killelea discussed balancing high-risk screening (which usually includes MRI) with the concerns about gadolinium toxicity. Gadolinium is a “rare earth heavy metal”, and is used in the contrast material that is administered (using an intravenous line) when breast MRI is performed. Acute allergic reactions are uncommon but as gadolinium is excreted through the kidneys, there are concerns about the potential for kidney damage especially in patients with pre-existing renal insufficiency. Nephrogenic systemic fibrosis (NSF) is an unusual condition that results in progressive deposition of gadolinium in the skin. It has also been found that the number of exposures to the linear form of gadolinium (as opposed to macrocyclic, which is what is most commonly used with breast MRI) correlates with increasing deposits in the brain. More research is needed to determine if this leads to an increased risk of Parkinson’s or other diseases. Studies evaluating “fast” MRI protocols are ongoing but they still use gadolinium contrast. Some work is being done with non-contrast MRI and Dr. Killelea noted that it shows some promise in detecting certain lesions. 

In the session on Ethical Issues in Breast Cancer Surgery, Dr. Rachel Greenup discussed how to manage the situation when the principles of respect for patient autonomy conflict with the standard of care. She noted that patient autonomy allows for us (as physicians) to educate but not to decide care for patients, and that poor physician-patient communication is a key factor in patients opting for non-standard care. Factors associated with patients declining standard therapy include a negative first experience, an uncaring / insensitive / unnecessarily harsh oncologist, fear of side effects, and belief in the efficacy of alternative therapy.  In regards to endocrine therapy for breast cancer, she noted that unmanaged side effects are a significant contributor to stopping therapy. She also presented data showing poorer outcomes in patients who declined standard therapy, and that many, when faced with disease progression, did then opt for conventional treatment. She recommended that physicians review and present evidence to their patients in an understandable way, taking time to acknowledge fears and address patient barriers to treatment, provide time to adjust to diagnosis, suggest a 2ndopinion, and avoid abandonment or fear tactics. She also suggested that physicians be more open (when medically safe) to the combination of alternative and standard therapy. She stressed that patient autonomy is the priority, and that open communication can help align patient-centered care with evidence-based care. 

Dr. Terry Sarantou discussed the ethical issues of obtaining informed consent when performing a new surgical procedure, noting that there is FDA oversight for new drugs and surgical devices, but not for surgical procedures. He stressed that informed consent is a communication process, not a form to be signed. 

Recognizing the role that surgeons play in the current opioid crisis, Dr. Sarah DeSnyder discussed proper prescribing of narcotics in breast surgery. There was also an abstract presentation by Dr. Betty Fan (abstract 5808940, page 27) on this subject. She noted that women who expected postoperative pain or those who reported higher preoperative distress used more postoperative opioids for pain management. She stressed that physician and trainee education about proper prescribing is critical as is setting patient expectations for postoperative pain and providing non-narcotic options. The use of nerve blocks, long-acting local anesthetic agents, acetaminophen (Tylenol) and ibuprofen were also discussed. 

Photographs are an important part of breast and reconstructive surgery to document results both for patient and physician education as well as for quality assurance, and Dr. Toan Nguyen reviewed some of the ethical, legal and technical considerations to protect patient confidentiality and privacy. The ASBrS statement on this issue has been published in the Annals of Surgical Oncology.

In the session covering New Perspectives on Old Problems, Dr. Lee Wilke noted that with improved surgical techniques, breast conservation is now appropriate for select patients with more than one tumor in the breast. She did note that in up to 20-30% of patients with more than one tumor in the breast, the tumors are different subtypes, which may have implications for therapy – so pathologic analysis needs to be performed on all lesions. Dr. Stephen Grobmyer reviewed the current literature on local (in-breast) recurrence, noting that repeat breast conservation may be appropriate in some patients. However, if repeat radiation is performed, there is a higher risk of skin toxicity and potentially unacceptable cosmetic results. In addition, for left-sided breast cancers, repeat radiation raises concerns about cumulative radiation damage to the heart. Repeat lumpectomy without radiation is associated with a 20-40% risk of local recurrence. IORT may be utilized in some patients, but studies are ongoing and data is limited.

Dr. David Euhus discussed that genetic testing does not only potentially impact the surgical procedure that is recommended, but may influence the decision for radiation therapy as well as systemic therapy. In addition, results of genetic testing may impact surveillance for additional breast or other cancers in the patient as well as recommendations for family members. The ASBrS recently updated their genetic testing guideline, recommending that genetic testing be considered for newly diagnosed breast cancer patients. (Additional perspective)

In the session on Benign Breast Disease, Dr. Jane Mendez reviewed breast fistulas (persistent drainage through the skin) and infections, and Dr. Vincent Reid reviewed some of the non-malignant masses that can develop in the male breast. Dr. Katrina Mitchell, who is a breast surgeon as well as a certified lactation consultant, provided recommendations for management of post-partum patients who develop mastitis or breast abscess. One of the key recommendations was that patients should continue breast feeding (better than pumping for keeping the breast empty) and that patients do not need to “pump and dump” the milk while on antibiotics. 

Dr. Stephanie Valente discussed breast pain, which is a common problem that frustrates both patients and physicians. Pain is a symptom of breast cancer in less than 2% of cases.  Suggestions for treatment include decrease caffeine, nicotine, and dietary fat intake, and consider supplementation with essential fatty acids such as evening primrose oil (EPO) or vitamin E. However, she noted that that some studies show that EPO and vitamin E are no better than placebo. Both flaxseed and chasteberry have shown to be effective. Diclofenac (a non-narcotic pain medication) gel can be effective but it needs to be used for several weeks before improvement is seen and it is expensive. In severe cases, danazol (an androgen hormone) or tamoxifen can be used but are associated with significant side effects.

There were several sessions on oncoplastic surgery. Oncoplastics refers to combining oncologic (cancer) surgery with attention to cosmetic outcomes. Basic principles include placing the incision in the least conspicuous place and closure of as much of the breast tissue once the tumor has been removed as possible to minimize, or preferably avoid, a depression in the area. More advanced techniques include rotation flaps and mastopexy (lift) that may be performed by breast surgeons or breast surgeons collaborating with their plastic surgical colleagues. There was also a session discussing some of the advanced microvascular procedures that are being studied to treat lymphedema as well as a video session showing some basic techniques to perform a better (flat) closure for patients undergoing mastectomy without reconstruction. 

The keynote address was delivered by the actress Kathy Bates. Ms. Bates underwent a bilateral mastectomy for breast cancer and has bilateral arm lymphedema. She is a spokeswoman for the Lymphatic Education and Research Network, working to educate, support, and advocate for patients who have lymphedema. She delivered a moving and unique address to the group, combining science and her personal patient perspective. An abstract (abstract 581304, page 22) presented during the meeting demonstrated that postoperative surveillance with bioimpedence spectroscopy compared to tape measure resulted in a 10% decrease in the number of patients requiring complex decongestive physiotherapy. However, these results, which were a planned interim data analysis, did not reach statistical significance.

The new ASBrS screening mammography guidelines were released at the meeting. They recommend formal risk assessment starting at age 25 and a risk-based approach to screening, as well as annual mammography starting at age 40 for average-risk women. (Additional commentary)

All of the research abstracts and posters can be found here. There were many interesting and thought-providing presentations, but it is important to remember that abstracts represent incomplete data and have not been subject to the peer-review process. The oral abstracts that were presented will be published in manuscript form later this year. The poster gallery can be found here (not all posters have been uploaded by the presenters).

As usual if anyone is interested in one of the articles referenced but does not have access, or wants additional information, please send your email address to me: contact at drattai dot com and I will be happy to respond.

This post has not been endorsed by the American Society of Breast Surgeons.