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: ajscheitler@ucla.edu

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! 

21 October 2019

Especially during October, when everything seems to be painted pink, it’s easy to overlook the fact that breast cancer is a disease of women and men. Male breast cancer accounts for 0.6 – 1.0% of all breast cancer cases. In the US, approximately 2600 men will be diagnosed with breast cancer each year. The lifetime risk is about 1 in 1000, versus 1 in 8 for women. Male breast cancer accounts for approximately 500 deaths in the US per year. Risk factors include increasing age, family history including BRCA gene mutations, obesity, alcohol intake, prior chest wall radiation, and low androgen hormone levels.

Male breast cancer tends to be diagnosed in later stages compared with breast cancer in women, and previous studies have come to conflicting conclusions about whether the poorer outcomes are due to higher stage at diagnosis or other factors. A study recently published in JAMA Oncology* looked at mortality rates among men and women diagnosed with breast cancer. The researchers used the National Cancer Database (NCDB) and compared men and women who were diagnosed with breast cancer between January 2004 – December 2014. Their data analysis included approximately 16,000 men and 1.8 million women. Some of the key findings:

  • Mean age at diagnosis was 63.3 for men and 59.9 for women
  • 3-year survival was 86.4% for men and 91.7% for women
  • 5-year survival was 77.6% for men and 86.4% for women
  • Overall survival was 45.8% for men and 60.4% for women

Men diagnosed with breast cancer were older, were more likely to be diagnosed at advanced stages, and were less likely to receive conventional therapy. However, differences in survival persisted even after controlling for clinical characteristics of the disease, age, race and ethnicity, and access to care. Limitations of this study are that cause of death could not be determined (so it is not clear if all of the deaths are related to breast cancer) and the NCDB does not contain information on recurrence, BRCA gene status, adherence to treatment recommendations, and other medical conditions. However, the researchers concluded that male sex remained a significant risk factor for poorer outcomes, which suggests that there are biological differences in male versus female breast cancer. 

Another study recently published in the journal Cancer* also used NCDB information to look at treatment trends for men treated for breast cancer from a similar time period. The authors evaluated approximately 10,000 cases and noted that:

  • 24% underwent breast conserving surgery (lumpectomy)
  • 70% of those undergoing lumpectomy received radiation
  • 44% of patients received chemotherapy
  • 62% of those with estrogen receptor positive (ER+) breast cancer received endocrine therapy
  • 35% of those with ER+ / lymph node negative breast cancer had Oncotype Dx testing on their tumor to help determine need for chemotherapy

These findings are consistent with a point made in the JAMA Oncology study noting that men were less likely to receive conventional therapy – for example only 62% with ER+ breast cancer received endocrine therapy and only 70% of those undergoing breast conserving surgery were treated with postoperative radiation therapy. Some of the same limitations apply to this study, in that reasons for differences in therapy could not be determined, and there was no information on disease recurrence.

A few other important points to make about male breast cancer:

  • Most male breast cancer presents as a lump, but as in women, most lumps are not cancerous. It is important that a proper evaluation (usually including a mammogram and ultrasound, and possibly biopsy) be performed for any change
  • As in women, male breast cancer may present with nipple discharge (especially blood), “puckering” or “pulling in” of the skin, or severe redness of the skin which can be mistaken for infection – the latter may indicate a more aggressive type of breast cancer known as inflammatory breast cancer
  • ALL men with breast cancer, and anyone with a family history of male breast cancer, should undergo genetic counseling and testing. As in women, most cases of male breast cancer are “sporadic” (not related to an inherited mutation), but men with breast cancer are more likely to carry deleterious BRCA (especially BRCA 2) mutations
  • Men who carry a deleterious BRCA mutation have an approximately 8% lifetime risk (to age 80) of developing breast cancer. So while that is considered “high risk” for men, they are still more likely to NOT develop breast cancer. We do not currently recommend prophylactic mastectomy in men who carry a deleterious BRCA mutation but who have not been diagnosed with breast cancer
  • Men who carry a deleterious BRCA mutation are also at higher risk for prostate cancer, melanoma, and pancreatic cancer

Men with breast cancer are usually treated using the same protocols that are used for women. Unfortunately there is limited data to support this. Male breast cancer is not common, so it is challenging to enroll large numbers of patients in clinical trials. However, men have historically been excluded from many breast cancer clinical trials, so how can we even make progress? The US FDA has recently issued draft guidelines encouraging the inclusion of male breast cancer patients in clinical trials – this is certainly a step in the right direction.

*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:

15 October 2019

Mastectomy (breast removal) rates continue to increase in the US. While reconstructive surgery is commonly performed after mastectomy, some patients opt to “go flat” or have no reconstruction. Some patients who have had reconstruction need to or choose to have the reconstruction reversed.

The aim of this study is to survey the “Going Flat” patient communities to assess patient satisfaction with their decision and results. 

This survey is being conducted for research purposes. It is a UCLA research survey. 

Patients should meet one of the following criteria to participate:

  • Single or double mastectomy for any reason (including if lumpectomy was performed first) and decided not to have reconstruction (decided to “go flat”)
  • Single or double mastectomy for any reason (including if lumpectomy was performed first), initially had reconstruction but then had reconstruction reversed or removed for any reason

This survey is voluntary and is completely anonymous.  No identifying information, including internet protocol (IP) addresses, will be collected. There is no industry funding or sponsor for this survey. The survey should take approximately 15 minutes to complete. We value your time and your opinions. The anonymous data will be securely stored by the principal investigator and may be used for future research studies.

To participate in the survey, please click this link or cut and paste it into your web browser: https://uclahs.az1.qualtrics.com/jfe/form/SV_7UPj6wVtZev9UGx

For questions regarding this study, you may contact principal investigator Dr. Deanna Attai

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 

16 September 2019

The US Food and Drug Administration (FDA) has issued a safety announcement about a “rare but severe” lung inflammation that can result from the use of any of 3 breast cancer medications – palbocilcilb (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). These 3 medications are in a class of drugs called cyclin-dependent kinase (CDK) 4/6 inhibitors. They are used in estrogen receptor positive (ER+), Her2/neu negative metastatic (Stage 4) breast cancer, and work by interfering with cell division

The FDA announcement states that “the overall benefit of CDK 4/6 inhibitors is still greater than the risks when used as prescribed.” Palbociclib has been FDA-approved since 2015, and ribociclib and abemaciclib hae been approved since 2017. In evaluating studies of all 3 of the CDK 4/6 inhibitors, the FDA alert noted that 1-3% of patients taking these medications developed severe lung inflammation, and less than 1% died due to the condition.

The FDA recommended that patients notify their physicians immediately if they develop difficulty or discomfort with breathing or shortness of breath while at rest or at low activity when taking any of these medications. The FDA alert notes that there no specific risk factors that have been identified to determine how likely an individual patient is to develop severe lung inflammation while taking one of the CDK 4/6 inhibitors. They recommended that physicians routinely monitor their patients for lung symptoms that could indicate the development of severe inflammation. They also recommended that any side effects be reported to the FDA MedWatch Program. The alert noted that common side effects include “nausea, vomiting, diarrhea, constipation, decreased appetite, abdominal pain, infections, low red blood cell counts, low white blood cell counts, low platelet count, headache, dizziness, hair thinning or loss, rash, tiredness, and weakness”. I will post an update as more information becomes available.

Additional Information:

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.

24 July 2019

This morning, the US FDA announced that it was recommending that specific models of breast implants manufactured by Allergan be removed from the market due to concerns about breast implant associated anaplastic large cell lymphoma (BIA-ALCL), a form of cancer. Allergan responded by announcing a worldwide recall of BIOCELL textured breast implants.

The FDA announcement notes that 573 cases of BIA-ALCL have been diagnosed worldwide, and the majority of the cases (481) have been linked to Allergan implants. While BIA-ALCL is thought to be curable by removing the implant and capsule, the FDA announcement reports that 33 patients have died. In 13 of the cases (of patient death) where the implant manufacturer was known, 12 patients had Allergan implants. The FDA announcement was prompted by information received since March 2019, when the FDA issued a letter to healthcare providers and held a public meeting to increase awareness of BIA-ALCL and to request that suspected cases be reported.

The plastic surgeon’s office typically keeps a record of the type of implant placed. Today’s FDA announcement stated that the majority of implants placed in the US are NOT the textured form, and that the specific type of Allergan implant implicated accounts for about 5% of all implants placed in the US. BIA-ALCL is not common, and typically presents with rapid accumulation of fluid (that a patient would notice as swelling) sometime after placement. As always, report any changes to your physician.

Update after 7/25/19 FDA call: I had the opportunity to sit in on a call with the FDA and several other surgical societies this morning and a few points were made:

  • The implants implicated in the recall were not marketed in the US prior to March 2000.
  • A small percentage of cases of BIA-ALCL have occurred in patients who have no history of textured implants.
  • Tissue expanders, the temporary “spacers” that are often used prior to stretch the skin and muscle, are often textured. They are not usually left in place for more than a few months, but the FDA did not have any information or insights as to whether these might be the cause of BIA-ALCL in patients with no history of textured implants.
  • The FDA is not recommending removal of implants in asymptomatic patients. They stressed that if implants are removed, the implant capsule (the fibrous scar tissue that normally forms after implant placement) also needs to be removed, because that is where the ALCL develops.
  • It was discussed that there is no “early detection” for BIA-ALCL, and that patients may not be comfortable with a “watch and wait” approach.
  • Concerns were raised about insurance coverage for implant removal and replacement, especially in patients who are asymptomatic. The FDA commented that insurance coverage issues are out of their scope of practice but they recognize the problem. They did note that they had met with patient advocate groups earlier today
  • All of the representatives from the surgical organizations that were on the call agreed that education of their members as well as the larger physician community is necessary. A representative from the American Society of Plastic Surgeons noted that they have been educating their members for some time and have patient resources on their website. They also stressed that if patients note any changes, they should seek out a board-certified plastic surgeon
  • Symptoms of BIA-ALCL include the sudden development of swelling (due to fluid accumulation) with or without a mass. Any changes should be promptly reported.