07 April 2020

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 SurgeonsAmerican 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.

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

18 February 2020

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

10 February 2020

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.

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

19 December 2019

study recently published in the Journal of Clinical Oncology* found that the use of some vitamins and supplements before or during chemotherapy treatment for breast cancer was associated with increased recurrence and mortality rates.

Vitamins and supplements may interfere with or prevent the desired chemotherapy or radiation therapy effect of cell death, so it is common practice to advise patients to stop (or not to start) taking vitamins and supplements while undergoing treatment. The patients in this study were all undergoing chemotherapy for breast cancer, using the same medications, but with different dosing schedules. The treatment regimen was doxorubicin (also known as Adriamycin), cyclophosphamide and paclitaxel, commonly referred to as AC-T. Patients were surveyed on vitamin and supplement use prior to starting chemotherapy and after treatment. Median follow up was 8.1 years.

There were 1134 patients included in this study. 251 experienced a recurrence and 181 died – these patients were more likely to be older, Black, post-menopausal, have a higher body mass index, and have poorer tumor prognostic factors including 4 or more positive lymph nodes, and estrogen / progesterone receptor or Her2/neu negative tumors. 17.5% reported use of any antioxidant (vitamin A, vitamin C, Vitamin E, carotenoids, and co-enzyme Q12) during chemotherapy treatment and 44% used multivitamins.

The findings included:

  • Use of antioxidant supplements both before and during chemotherapy was associated with an increased risk of cancer recurrence and death, but the numbers were not statistically significant
  • The researchers were not able to determine if there was any specific relationship between the use of individual antioxidant supplements and risks of recurrence or death. There was a relationship with vitamin A but analysis for this supplement only included 5 patients
  • There were no relationships between use of antioxidants only before or only during treatment and outcomes
  • Vitamin B12 use both before and during chemotherapy was associated with increased risk of recurrence and death 
  • Iron use during chemotherapy was associated with higher recurrence risks as was use both before and during treatment 
  • Omega 3 use both before and during treatment was associated with increased recurrence risk but not death
  • There did not appear to be any association between recurrence or survival and the use of multivitamins, vitamin D, glucosamine, melatonin, acidophilus, folic acid, or vitamin B6

One of the authors’ conclusions was that “we found some support for the notion that use of dietary supplements during chemotherapy could have a negative impact on recurrence and overall survival.” It is important to stress that this was an observational study, which means direct cause and effect cannot be determined. Relative, not absolute risks, were reported. In addition, the number or women who reported taking non-multivitamin supplements was just under 200. While news reports noted that supplements were associated with a 40% increased risk of recurrence a weaker association with death, these numbers did not meet statistical significance. The authors noted that “a review… in 2010 concluded that insufficient evidence existed with regard to safety of dietary supplements to make recommendations, and that may still be the case.”

Despite the limitations of this study and the inability to draw firm conclusions, it is still recommended that patients who receive a recommendation for chemotherapy or radiation therapy inform their medical team of all vitamins and supplements that they are taking, and it still is considered best practice to avoid antioxidant supplements while undergoing treatment.

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

12 December 2019

A study presented at the San Antonio Breast Cancer Symposium last week provides more evidence to support the use of accelerated partial breast irradiation (APBI) after lumpectomy in selected patients with breast cancer.

Radiation after lumpectomy typically treats the entire breast (whole breast irradiation, WBI) and is usually administered daily for 3-6 weeks, depending on the protocol that is used. There are several techniques that treat only the lumpectomy site, which is where most recurrences occur. The techniques include the use of a single or multiple catheters, or an external beam approach. Most commonly, partial breast treatment is administered twice a day for 5 days. Of course, one of the concerns in using a partial breast technique is recurrence rates compared to the more standard WBI approach.

A large US-based study on partial breast irradiation was presented in 2018 and was recently published. The NSABP B-39 trial* included 4200 patients, randomized to WBI or APBI techniques. This study showed that APBI was “not equivalent” to whole breast irradiation but absolute differences in local recurrence rates were small (90 / 4% in the APBI group versus 71 / 3% in the WBI group). 

The current study (APBI IMRT Florence) was performed in Italy and included 540 patients. All were over age 40, had tumors ≤ 25mm in size, and surgical margins ≥5mm [note – current US national guidelines support “no ink on tumor” for a margin]. The findings included:

  • Local (in-breast) recurrence rates were 3.9% (9 patients) with APBI and 2.6% (6 patients) with whole breast irradiation and that difference was not statistically significant
  • Overall survival was 92.7% in the APBI group and 93.3% in the WBI group
  • Breast cancer-specific survival was 97.6% in the APBI group and 95.7% in the WBI group 
  • There were 7 patients in each group who developed metastatic breast cancer
  • There were fewer adverse events and better cosmetic results reported in the APBI group compared to the WBI group

The authors concluded that APBI is appropriate to consider in selected patients with “low risk” cancers. While the Italian study has only been presented in abstract form (we do not have the full dataset or manuscript yet), it adds to what we already know about this accelerated technique, which does seem to be a reasonable option in selected patients.

*If you are not able to access the full study 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

20 November 2019

One of the challenges in treating male breast cancer is that there are few studies specifically focusing on men. Breast cancer is much less common in men than in women (approximately 2600 versus 260,000 cases per year in the US). However, men tend to be treated using the same protocols that are used for women – even though we don’t know if that is the most effective approach.

For women with stage 1-2 breast cancers that are estrogen receptor positive (ER+) and Her2/neu not over-expressed (Her2-), additional tumor testing is commonly performed to determine whether or not chemotherapy would be of benefit. The Oncotype Dx test, one of several commercially available genomic tests, has only been validated in women. Researchers recently evaluated whether the Oncotype Dx test has the same prognostic ability in men as it does in women. 

The researchers used the National Cancer Database to identify women and men diagnosed with stage 1 and 2, ER+ and Her2- breast cancer between 2010-2014, for whom Oncotype Dx recurrence scores (RS) were available. 848 men and 110,898 women were identified. Associations between mortality and RS were determined. Overall mortality was 41 for men and 2527 for women. 

Findings included*:

  • Men had a higher proportion of RS ≤10 or ≥31 versus women
  • Use of chemotherapy increased with higher RS for both men and women
  • Among patients with RS ≥26, 70.9% of men and 74.8% of women received chemotherapy
  • In men, increasing RS were associated with increased likelihood of death up to a RS of 21, after which the risk plateaued
  • In women, RS was only associated with an increased likelihood of death above a RS of 23 
  • A concluding statement: “…RS is prognostic for total mortality in both male and female patients, but with distinct association patterns. Mortality increased in much lower ranges of RS for male than female patients with breast cancer.”

Some limitations of the database review were that only overall, not breast cancer-specific mortality could be assessed (so we do not know why the patients died), and there was no information on specific details of treatment or adherence to treatment. However, this study does provide some insights into the biological differences between breast cancer in men and women, and the researchers called for more study evaluating whether the RS is predictive of chemotherapy benefit in men with breast cancer.

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

AACR Press Release

13 November 2019

The UCLA Center for Health Policy Research (UCLA CHPR) is developing a report on metastatic breast cancer, with the goal to drive actionable change in policy and practice. On Monday November 18th, the community will be asked to provide their thoughts for the UCLA CHPR team as part of their research study. The goal is to hear from patients, healthcare providers, researchers, caregivers, and advocates about the different types of barriers and challenges that patients with metastatic breast cancer may encounter when seeking and undergoing treatment. 

No idea too small or idealistic – we want creative, actionable solutions! The information gathered in this research study will be shared more broadly with other stakeholders, advocates, and policy makers. Please add your voice to this important conversation! This study has been funded by the California Breast Cancer Research Program

The study team may be contacted by sending an email to: [email protected]

If you’ve never joined a tweet chat, click here for information on how to participate in the conversation.

Discussion topics will include: 

  1. What are the most significant healthcare communication barriers faced by patients with metastatic breast cancer? 
  2. What are the most significant barriers to obtaining appropriate palliative care faced by patients with metastatic breast cancer?
  3. What are the most significant financial barriers faced by patients with metastatic breast cancer?
  4. What are the most significant barriers to obtaining disability faced by patients with metastatic breast cancer? 
  5. What health system or policy actions do you recommend to address barriers these barriers to care?
  6. Any other comments or suggestions!