An abstract presented at last week’s virtual meeting of the American Society of Clinical Oncology focused on whether or not there is a benefit to surgery for the primary breast tumor in patients with metastatic, or Stage IV, breast cancer.

Metastatic breast cancer (Met-BC) is when the breast cancer spreads beyond the breast and underarm lymph nodes. Common sites of metastases include the lungs, liver, bones, and brain. Anyone diagnosed with breast cancer has the potential to develop metastatic disease, but approximately 5-10% of patients are found to have Met-BC at the time of initial diagnosis, known as de-novo Stage IV. In these patients, it has been controversial whether or not to recommend lumpectomy or mastectomy to remove the primary tumor. Some studies have shown a survival benefit when the primary tumor is removed, but widespread adoption of the results of these studies has been limited because in many of these studies, patients who underwent surgery were younger, healthier, and had a lower volume of metastatic disease compared with the general population of patients with Met-BC.

Dr. Seema Khan presented the results of the ECOG-ACRIN Research Group E2108 study. In this study, patients who had stable Met-BC (after 4-8 months of treatment) were randomized to either surgery or no surgery for the primary tumor. The two cohorts were well-matched for age, race, and breast cancer subtype. With a median follow up of 59 months, there was no improvement in overall survival or in progression-free survival. Local progression (cancer continuing to grow in the breast) was more common in patients who did not undergo surgery (25.6 versus 10.2% at 3 years). Health-related quality of life was significantly worse in those who underwent surgery at 18 months, but no differences were observed at the 6-month or 30-month assessment intervals.

During her presentation, Dr. Khan acknowledged that there may be situations where surgery for the primary tumor is a reasonable option in the setting of Met-BC. She noted that there is room for individualization, but stressed that as there is no survival benefit and no improvement in quality of life, surgery for the primary tumor in the setting of Met-BC should not routinely be performed. 

It is important to note that any medical meeting abstract, whether an oral presentation or poster, has been evaluated by the meeting program committee but has not been subject to rigorous peer review as would occur with a formal manuscript submission. Abstracts often do not include the full set of results, and additional findings may be included in the eventual publication, some of which may be different than those presented in the abstract. We look forward to the peer-reviewed publication when it is available. 

• ECOG-ACRIN E2108 press release
• ASCO Post
• ASCO Daily News

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Going Flat after mastectomy refers to not undergoing breast mound reconstruction after breast removal. Some patients are not candidates for reconstruction or it is not recommended, however many women may choose to “go flat” even when breast mound reconstruction is an option. This past October, we posted a research survey aimed at better understanding motivations to forgo reconstruction and to identify factors associated with postoperative satisfaction among patients who participate in online breast cancer communities.

The abstract and poster are now posted on the virtual meeting platform of the American Society of Breast Surgeons. Our findings include:

Demographics and timing of going flat:

• 940 women completed the survey, mean age was 53 (range 25 – 84)
• Most patients were white (94%), had private insurance (70%), and were from the US (74%) although 22 countries were represented
• 85% (801/940) did not undergo breast mound reconstruction at the time of mastectomy
• 15% (139/940) initially had reconstruction that was subsequently removed

 Top 2 reasons for going flat:

• 72% desire to avoid foreign body such as an implant
• 71% perceived lower complication rate from the surgery

Communication:

• Only 64% were initially offered going flat as an option
• 30% felt that their surgeon did not support their decision to go flat

Satisfaction with outcome:

• 74% agreed or strongly agreed that they were satisfied with their surgical outcome
• Age, race, bra cup size, and history of prior breast mound reconstruction were not associated with postoperative satisfaction
• Strongest predictors of satisfaction were having adequate information about surgical options and surgeon support of the patient’s decision to go flat

Our findings reveal a need for additional research into factors that impact patient satisfaction as well as for surgeon education on how to optimally support women who are not interested in breast mound reconstruction.

It is important to note that any medical meeting abstract, whether an oral presentation or poster, has been evaluated by the meeting program committee but has not been subject to rigorous peer review as would occur with a formal manuscript submission. Abstracts (including ours) do not include the full set of results. It is not unusual for additional findings to be included in the eventual publication, some of which may be different than those presented in the abstract. However, we feel that these results are an important starting point for better understanding of patient motivations for going flat, and also point to a need for improved communication on the part of surgeons. We are in the process of completing a full analysis of the data and look forward to sharing the peer-reviewed publication when available. 

On behalf of my co-authors, we would like to thank all who shared and participated in the survey!

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I was asked to help the UCLA Jonsson Comprehensive Cancer Center team develop some infographics to help answer some common questions that patients with cancer may have regarding their treatment, office visits, and risk of infection. As always, good communication with your medical team is important – so reach out and ask if you have questions or concerns.

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A new drug was recently approved by the US Food and Drug Administration (FDA) for the treatment of metastatic breast cancer – breast cancer that has spread to other areas of the body, such as the bones, liver, lungs or brain. Sacituzumab govitecan (Trodelvy), which is given by intravenous infusion, was granted accelerated approval to treat metastatic triple negative breast cancer in patients who have already been on 2 prior treatments for their disease. 

Triple negative breast cancer accounts for approximately 15% of breast cancers. It is more common in younger patients, African Americans, and those with a BRCA1 gene mutation. It can be very challenging to treat since there is no specific cellular target, such as the estrogen receptor or Her2/neu protein. Patients with triple-negative breast cancer very commonly receive chemotherapy but the disease may come back or progress despite aggressive treatment.

Sacituzumab govitecan is an antibody-drug conjugate, which is an antibody that is combined with a chemotherapy drug. The antibody targets a protein (trophoblast cell surface antigen-2, or trop-2) on the surface of the cancer cell, and the chemotherapy drug causes breaks in the tumor cell DNA, which leads to cancer cell death. The FDA approval was based on a non-randomized (meaning all patients received the study drug) study of 108 patients who were experiencing disease progression despite receiving between 2 – 10 prior treatment regimens. Among the study participants, approximately 33% experienced a partial or complete tumor response to the medication. Median duration of treatment response was nearly 8 months. Severe adverse reactions included diarrhea, neutropenia (low white blood cell counts), anemia (low red blood cell counts), fatigue, nausea and vomiting. 2 patients stopped treatment due to side effects.

Any advance in the treatment of metastatic breast cancer is welcome news. It is hoped that as new drugs are developed, a longer-lasting response to therapy will be achieved. 

Additional Information:

• FDA News Release
• ASCO Post
• MedPage Today

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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:

• ASCO Post: FDA Approves Tucatinib
• FDA News Release

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Many of us are struggling to adjust to the changes we have had to make due to the COVID-19 (coronavirus disease 2019) pandemic. For those newly diagnosed with or undergoing treatment for cancer, there is an added level of anxiety and uncertainty, especially as national medical societies have made recommendations to curtail office visits, screening mammograms, breast cancer surgery and other treatments. 

It is important to understand that these guidelines and recommendations are being made in the best interest of both individual and general public health. It has become clear that people who are seemingly healthy (no cough, fever, or other symptoms of illness) may in fact carry the SARS-CoV-2 virus and may infect others. “Social distancing” and “stay at home” recommendations can help reduce the number of people infected or can at least help to “flatten the curve” – spread the number of infected out over a longer period of time, to lessen the impact on the healthcare system. 

Many breast surgeons and oncologists have transitioned to telephone and video encounters – but we are still available to see patients who need an examination or treatment. The American Society of Breast Surgeons and the American College of Radiology have issued a joint statement recommending that screening mammograms be put on hold for now. Screening studies are those performed in asymptomatic individuals – those without any lump or other concerning problem. Most facilities are still performing diagnostic imaging (workup of a problem) and biopsies. As noted in the statement, “there is no evidence that delaying screening mammography for the proposed short time period will affect mortality but there is plenty of evidence that being exposed to the coronavirus can impact mortality.”

While streets and restaurants are empty in those communities practicing “social distancing”, it’s a different story at hospitals. Although most areas in the US have not yet reached their peak incidence in terms of SARS-CoV-2 cases, many emergency departments and intensive care units are full. The healthcare system is dealing with a shortage of basic protective equipment such as masks, gowns, and gloves. In addition, medications are on backorder – medications that are needed for patients who require use of a ventilator due to critical illness are the same ones used for general anesthesia during surgery. Despite best efforts to isolate patients known to be infected, some will develop the infection while in the hospital. Surgical patients who either have or develop SARS-CoV2 infection have higher mortality rates. Physicians are becoming infected, removing them from the pool of available healthcare workers.  

Keeping one patient out of the operating room can free up personnel, equipment, and medications for someone who has become critically ill – and may be the difference between their life and death. Therefore, most hospitals have drastically cut the number of “elective” surgeries that are being performed. 

For facilities, there are 3 phases that have been described:

• Phase I is considered the semi-urgent, or preparation phase, where hospital resources have not been exhausted, ICU beds and ventilators are available, and the number of cases in the community are not rapidly increasing
• Phase 2 is an urgent setting, where the facility has many SARS-CoV-2 infected patients, there are limited ICU beds, ventilators and protective equipment, or the number of cases in the community are rapidly increasing
• Phase 3 is when all hospital resources are routed to infected patients, and there are no available ICU beds ventilators, or protective equipment.

While an individual may not consider their pending surgery for cancer or risk reduction to be truly “elective”, the American College of Surgeons, American Society of Breast Surgeons, and the Society of Surgical Oncology have guidelines for breast surgery that are based on the type of procedure, taking into account the situation at an individual healthcare facility or system. Most have similar recommendations:

• Surgery for benign breast conditions and for risk reduction is not recommended at this time. This includes contralateral prophylactic mastectomy (removal of the opposite, “healthy” breast during surgery for cancer)
• For patients with breast cancer, decisions are made based on local resources as well as the specific subtype of cancer
• When the decision is made to proceed with surgery, it is recommended to perform the minimum possible, under local anesthesia and sedation (versus general anesthesia) if at all possible – for example some patients who desire mastectomy may be recommended to undergo lumpectomy (if technically possible) as a temporizing measure
• Lengthy reconstructive procedures (such as autologous or “free” flaps) are not recommended by the American Society of Plastic Surgeons
• If appropriate based on tumor biology, chemotherapy or endocrine therapy prior to surgery is recommended

These are guidelines – they are no substitute for personalized recommendations by your medical team who best know your situation as well as that of their hospital. No one takes lightly the impact of delaying surgery – both from the standpoint of treating the cancer as well as the added psychological stress on the patient and their family. However, we are dealing with a novel disease and the full impact, devastating already, has yet to be seen. While it is hoped that these restrictions will not be in place for longer than 1-2 months, many areas of the country are not expected to reach their peak SARS-CoV-2 incidence for several weeks. Please reach out to your medical team, mental health provider (if you need or have one) and each other – virtually of course – if you need help, answers or support. Stay home and stay well.

• Additional Resources:
• American Society of Clinical Oncology Coronavirus Resources
• Facing Our Risk webinar recording (registration required)
• Facing Our Risk webinar slides
• Breast Cancer Research Foundation podcast with Dr. Judy Garber
• US Center for Disease Control
• World Health Organization
• Why You Should Ignore all that Coronavirus-Inspired Productivity Pressure – this article is geared towards those in academics, but I found the information and advice on adapting to crisis very helpful and can apply to almost anyone

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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

• Additional Information:
• ASCO Post
• Journal of Clinical Oncology editorial

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The American Society of Clinical Oncology recently published a guideline for the management of male breast cancer* (and I was proud to serve on the guideline consensus panel).

Breast cancer in men accounts for approximately 1% of all breast cancer cases. Outcomes are known to be worse compared with those in women, in part due to later diagnosis. Unfortunately, men are often excluded from breast cancer clinical trials, so they are most often treated using the protocols approved for women. However, it is unclear if this is the best option in every situation. The US FDA has recently called to include men in studies of breast cancer treatment, even if anticipated enrollment is low. This is a necessary step so that progress can be made.

*If a copy of the full guideline is desired, please reach out: contact at drattai dot com

The post Male Breast Cancer Guidelines appeared first on Dr Deanna Attai.

Our publication “Proposing a Bill of Rights for Patients with Cancer” was just published! Many thanks to my co-authors, and to all of the patients who inspired this piece.

The post A Bill of Rights for Patients with Cancer appeared first on Dr Deanna Attai.

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

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