17 August 2020

Last year, we asked the online breast cancer community to participate in a survey to assess experiences with endocrine therapy (ET). We are proud to announce that the study has now been published, in the Journal of Cancer Survivorship*.

First of all, I would like to thank all of the participants – we surpassed our accrual goals and this is the largest survey of ET use by patients who participate in online breast cancer communities! 

About the respondents:

  • 111 respondents did not start the recommended ET, and concern about side effects was the primary reason
  • Of those who took ET (2407), 2353 were women and 54 were men
  • Most of the women (74%) were post-menopausal
  • Mean age at diagnosis was 50 for women (range: 23-82) and 54 for men (range: 24-73)
  • Most (87%) were diagnosed at Stage 1-3
  • 100 (4.2%) were diagnosed with de novo Stage 4 / metastatic breast cancer
  • 12% of those diagnosed at an early stage eventually developed Stage 4 / metastatic breast cancer

Treatment:

  • Aromatase inhibitors (AIs) were the most commonly used medication
  • 91% of respondents reported at least one class of side effect that they felt was related to treatment (92% of women and 74% of men)
  • Musculoskeletal and general physical changes (such as weight gain and unhappiness with body image) were the side effects most commonly reported by women
  • Men most commonly reported sexual and cognitive / mood side effects
  • 33% (33% of women and 50% of men) discontinued therapy early
  • 9% reported that they took treatment breaks or discontinued therapy early either without informing their medical team or against their medical team’s advice

Side effect management:

  • 3 classes of side effect management strategies were felt to be most helpful:
    • Healthy diet, exercise, physical therapy
    • Complementary therapy such as yoga, acupuncture and meditation
    • Vitamins, supplements and herbs including medical marijuana 
  • Only 41% of respondents noted any relief from side effect management strategies

Medical team communication: (multiple responses permitted so this category did not add up to 100%)

  • 70% felt supported by their medical team in attempting to discuss side effects
  • 32% were made to feel that they should be better able to handle side effects or that the side effects were not related to treatment
  • 7% did not discuss side effects with their treatment team, feeling that there were more important issues to discuss, that there was not enough time, or they did not feel comfortable

Some other findings:

  • Respondents with early-stage and metastatic breast cancer reported similar side effects and management experiences, even though these two groups of patients have very different supportive needs
  • Men who responded to our survey were less likely to report side effects but more likely to discontinue therapy early compared to women – more information is needed about the experience of men with breast cancer and those taking endocrine therapy

Clearly, there is room for improvement in terms of medical team support and understanding. In addition, as only 41% of respondents noted any relief from side effect management strategies, we need more effective treatments for ET-related side effects. Thank you to all who participated in this survey! We are hopeful that your responses and comments will inspire researchers devote more time to addressing these important issues.

*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

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

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:

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.

17 July 2019

There are no standard guidelines for mammographic screening for men who have no symptoms (such as a lump), even if they are considered to be at high risk for developing breast cancer. A study recently published in Breast Cancer Research and Treatment* evaluated the performance of screening mammography in asymptomatic high risk men.

The researchers reviewed a prospective institutional database at the Memorial Sloan Kettering Cancer Center, evaluating cases from 2011 – 2018. 827 men underwent mammography during that time period, but 80% were excluded from evaluation for this study as they underwent imaging due to the presence of a mass or other symptoms. Data from 163 asymptomatic patients, considered high risk due to a family and/ or personal history of breast cancer or the presence of a deleterious genetic mutation, was analyzed. 

Of the 163 men, 77% had personal history of breast cancer and 44% had a family history of breast cancer. 15% had deleterious BRCA mutations. Most of the genetic mutations (83%) were in the BRCA2 gene, as expected.

Over the 7-year time period, 806 screening mammography examinations were performed. The majority (792 studies, 98%) were BIRADS 1 or 2, indicating a normal study or benign findings. 10 (1.2%) were BIRADS 3 indicating a “probably benign” finding. Upon follow up, all of these patients were considered to have benign findings. 4 men had BIRADS 4 or 5 findings indicating suspicious or highly suspicious findings for which biopsy was recommended, and all were diagnosed with invasive ductal breast cancer.

Breast cancers in men are often diagnosed at more advanced stages than in women, and as a result, outcomes may be poorer. The authors noted that while mammographic screening has not been shown to reduce breast cancer mortality rates (the reason screening is performed) in men, the detection rate in this high-risk population (4.96 per 1000 examinations) is comparable to the breast cancer detection rate from screening mammography in average risk women. There were no false-positive (“false alarm”) biopsies in this group. The authors acknowledged one of the primary limitations of their study, the relatively small number of patients, and called for larger studies to confirm their findings. They concluded that their study “suggests that screening mammography should be performed in men at increased risk for 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

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: [email protected]; 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: [email protected]; or by mail: Box 951406, Los Angeles, CA  90095-1406

Research Survey Link

7 April 2019

The Society of Surgical Oncology held their annual meeting in San Diego, CA from March 27-30, 2019. Approximately 1700 surgical oncologists were in attendance. As the organization is geared towards the entire field of surgical oncology, only a portion of the meeting covered breast cancer. Here are some of the highlights:

Genetic Testing and Management
Dr. Judy Garber – Dana Farber
Updates in Testing and Management of BRCA Mutations
BRCA Mutation information from the National Cancer Institute
– Consider repeat testing if original genetic testing was performed prior to 2012 as more genes as well as pathogenic mutations have been discovered
– NCCN guidelines for breast cancer surveillance in BRCA 1/2 mutation carriers:
o Clinical breast exam every 6-12 months starting at age 25
o Annual MRI age 25-75 (individualize after age 75)
o Annual mammogram age 30-75 (individualize after age 75)
– NCCN guidelines for breast cancer prevention in BRCA 1/2 mutation carriers: discuss mastectomy, discuss tamoxifen
– Premenopausal BRCA mutation carriers who undergo oophorectomy experience breast cancer risk reduction. The level of breast cancer risk reduction in BRCA1 carriers is lower than in BRCA2 carriers as BRCA1-associated tumors are more likely to be triple negative
– Prenatal genetic testing is available in mutation carriers, and may be used for selective reproduction
– BRCA 1/2 mutation status does not impact breast cancer outcomes; tumor biology impact on outcomes is independent of mutation status
– BRCA 1/2 are DNA repair genes. Tumors associated with BRCA 1 tend to be triple negative and tumors associated with BRCA 2 tend to be ER/PR+, Her2- (but all combinations have been seen)
– Clinical trials are evaluating the use of cisplatin chemotherapy in patients with BRCA mutations – cancer cells are not able to repair DNA-induced chemotherapy damage due to the defective BRCA gene
– PARP inhibitors interfere with DNA repair and have traditionally been used to treat ovarian cancer. Small studies show some effect in breast cancer in the setting of BRCA mutations. Larger studies are ongoing. So far they only seem to work in breast cancer when there are BRCA mutations
– A challenge to treatment with PARP inhibitors is that there are many mechanisms of resistance, and tumors demonstrate a variable response to therapy – tests are being developed to predict response
– Lurbinectedin – a drug from sea slugs (!) may have some effect
– A very interesting comment – Dr. Garber noted that DNA breaks may be immunogenic, so there may be a role to combine PARP inhibitors and immunotherapy treatments
– Denosumab, a RANK-ligand used for bone protection in breast cancer patients, may have breast cancer risk-reducing activity – a randomized trial is pending to assess its activity as a preventative agent

Thuy Vu, Genetic Counselor – Wake Forest
What Genetic Test Should I Order?
– Once the appropriate patient for genetic testing has been identified, how to decide what lab to use? Consider lab experience, as well as cost and insurance support
– Patients with a complicated family history (multiple different cancers in scattered relatives), absent family history (adopted), and evidence of multiple cancer syndromes will benefit from NGS (next-generation sequencing) genetic panel testing
– A disadvantage of broad genetic panel testing is that there is currently incomplete information on all of the mutations that may be identified. Risk for cancers unrelated to the current diagnosis may be identified. In addition, there will be an increased prevalence of variants of uncertain significance (VUS)
– She noted to use caution when patients bring in test results from ancestry.com and similar companies – these sites often assess for SNPs (single nucleotide polymorphisms), which is not the same as testing for a genetic mutation, and full genetic testing may need to be repeated
– She acknowledged that there is a shortage of genetic counselors, even in large university centers. Many testing companies and labs now have associated genetic counselors, and there are some independent companies offering telephone counseling services

Dr. David Euhus – Johns Hopkins
ATM, CHEK2 and Other Genes
– While multiple gene mutations influencing breast cancer risk have been identified, they do not all convey the same level of risk
– As testing for multiple genes has increased, BRCA mutations are no longer the most common mutations found
– High risk genes include BRCA 1/2, TP53, PTEN, PALB2, STK11, CDH1
– Moderate risk genes include ATM, CHEK2, NBN, NF1
– These and other genes explain approximately 14-28% of genetic risk for breast cancer – most patients with a strong family history of breast cancer do not have an identifiable mutation
– There is a range of risk associated with all of the genes that in part depends on the mutation type – what type of damage does the mutation cause to the DNA. Family history of breast cancer can modify risk.
– For most of these patients, NCCN guidelines recommend annual MRI in addition to mammograms. Age to start supplemental screening depends on the mutation.
– He noted that increased screening for other associated cancers when there is no clinical benefit leads to patient harms – financial, emotional, and physical
– A good question from the floor about the role of ultrasound as supplemental screening (in addition to MRI) – Dr. Euhus states he uses 3D mammogram / tomosynthesis and does not use ultrasound unless the patient is pregnant / lactating

Dr. Kevin Hughes – Massachusetts General Hospital
What the Surgeon Needs to Know about Genetic Testing
– High cost of testing is not the problem – interpretation of the results is the challenge
– Assuming that approximately 10% of breast cancers are hereditary, over 51,000 breast cancers could have been prevented with testing
– For the breast surgeon, understanding BRCA 1/2 is not enough. There are many genes, each have different spectrum of associated cancers and associated risk; treatment needs to be individualized for the patient taking into account their specific mutation and family history
– He emphasized the point Dr. Garber made that if testing on a breast cancer survivor was performed prior to 2012, those patients should be re-tested
– Recent American Society of Breast Surgeons guidelines call for consideration of genetic testing in all breast cancer patients
– Dr. Hughes notes that this is already a standard recommendation for other cancers such as ovarian, pancreas and others
– The field is becoming more complicated – it is not expected that anyone can memorize this – go to the internet and look it up!

Resources:
ASK2ME – All Syndromes Known to Man Evaluator
ClinVar – look up specific mutations to see how they have been classified
PROMPT registry for patients with rare mutations

Breast Cancer Treatments in the Young and Elderly
Dr. Mina Sedrak – City of Hope
Treatment Strategies in Octogenarians with Early Stage, High-Risk Breast Cancer
– Incidence and mortality from breast cancer increase with age; the number of older adults in the US is increasing
– Breast cancer outcomes are often worse for older (as well as younger) women
– Older adults are underrepresented in cancer clinical trials – 1/3 of patients with breast cancer are over the age of 70, but only a small percentage of them are included in clinical trials
– Because of lack of clinical trial data in older women, patients may be under- or over-treated [DJA note – we have a similar situation in men with breast cancer].
– There is no universal definition of “old”. Aging is a continuous spectrum, and chronological age does not accurately predict functional age. The ASCO Guidelines Geriatric Assessment can help understand factors other than chronological age to predict morbidity and mortality. US Life Tables can also be used to estimate life expectancy, as well as ePrognosis. Estimation of life expectancy should be performed for all older patients before making a treatment plan
– How to best treat cancer in the elderly patient: it depends on life expectancy, aging concerns, risks / benefits of treatment and the potential impact of co-existing medical problems
– What risks can we modify and what are the patient preferences? There is no “one size fits all”

Dr. Tyler Chesney – University of Toronto
Adjuvant Radiotherapy for Older Women after Breast Conserving Surgery
– 4 randomized clinical trials addressed if elderly patients with low-risk breast cancer need radiation therapy after breast conserving therapy: NSABP B-21, A. Fyles, CALGB 9343, and PRIME II studies
o Meta-analysis of these 4 studies: 2387 patients across all trials, early stage breast cancer, hormone receptor positive. Addition of radiation therapy reduces local recurrence from 60 versus 10 / 1000 at 5 years. 2 trials had 10 year follow up, noting recurrence was 80 versus 20 / 1000 women.
o 3 of the trials provided data on axillary recurrence: absolute benefit was small, 12 versus 3 / 1000 women. No difference in distant recurrence or overall survival
– Prime I study showed that older women who underwent radiation therapy had increased fatigue over 5-10 years but similar overall health-related quality of life
– Accelerated partial breast irradiation may be an option, but some studies have shown higher local recurrence and poorer cosmetic result (depending on treatment method)
– While toxicities of radiation therapy have improved with more modern techniques, logistical concerns such as time, need to travel, and cost may be of higher concern for older women

Dr. Laura Dominici – Dana Farber Cancer Institute
Reconstruction and Body Image in Young Patients
– More than 13,000 women under the age of 40 are diagnosed with breast cancer annually in the US, approximately 7% of all new diagnoses
– Younger women newly diagnosed with breast cancer have been shown to have higher rates of anxiety and distress after diagnosis, they have historically received more aggressive treatment, and have a long survivorship period
– More aggressive surgery such as mastectomy does not lead to improved overall or breast cancer specific survival. Local recurrence is related to tumor biology, not age of the patient
– Mastectomy (single and bilateral) rates are rising, especially among younger women. Rates of reconstruction are increasing, as are rates of post mastectomy radiation
– A growing number of patients are “going flat” after mastectomy, opting for no reconstruction
– Dana Farber young women’s multicenter prospective cohort study: poorer satisfaction with breast-related, psychosocial and sexual well-being after unilateral and bilateral mastectomy. Other factors impacting poorer satisfaction include financial status, lymphedema, and the need for radiation
– 42% of women age 50 and younger (in the Dana Farber study) regret their surgical decision including primary surgery and reconstruction decision. Patients in this study were not asked what the actual regret was – doing too much or too little
– Important for patients to understand the oncologic outcomes of their decisions, and for physicians to promote shared decision making that takes into account patient preferences and concerns

Dr. Jo Chien – University of California, San Francisco
Fertility in Young Breast Cancer Patients
– 51% of women under age 40 with breast cancer are concerned about fertility; 38% desire to have future children but up to 97% are at risk of treatment related infertility. 26% report that their concerns about infertility affected their treatment decisions
– Loss of reproductive potential after cancer treatment results in worse long-term quality of life, unresolved grief / depression, reduced life satisfaction. Fertility preservation associated with less regret among young cancer survivors
– Less than 25% of general oncologists refer young breast cancer patients to fertility specialists
– Factors impacting risk of chemotherapy-induced ovarian failure: older age, baseline ovarian reserve, type of chemotherapy, and chemotherapy dose / duration
– Menses is not a surrogate marker for fertility. Fertility decline occurs ~10 years before onset of menopause. For women who remain premenopausal after chemotherapy, the majority enter menopause prematurely
– Options for fertility preservation: ovarian stimulation and cryopreservation of embryos / oocytes, GnRH agonists, and experimental techniques such as cryopreservation of ovarian tissue and immature oocyte retrieval with in vitro maturation
– Several studies have evaluated safety of letrozole-gonadotropin protocol in women with breast cancer and have found no difference in relapse-free survival. Very limited data on safety of ovarian stimulation in the neoadjuvant setting. In subset (82 patients – 34 stimulation / 48 controls) of I-SPY2 trial, no delay in start of neoadjuvant treatment and no significant difference in pCR or recurrence or mortality rates in patients who underwent ovarian stimulation before chemotherapy
– As discussed in the genetics session, Dr. Chien noted that for BRCA mutation carriers, pre-implantation genetic diagnosis is an option. Multiple follicles / embryos are required, often needing multiple stimulation cycles
– Observational studies suggest that pregnancy is safe after breast cancer.
– When is it safe to become pregnant after treatment? It comes down to patient’s underlying risk and likely their risk aversion. Dr. Chien prefers to wait to 2-3 years, but notes there is no data to support that. The POSITIVE trial is studying the impact of adjuvant endocrine therapy interruption to allow for pregnancy

Key papers
Dr. Kandace McGuire from Virginia Commonwealth University Massey Cancer Center provided an overview of 3 practice-changing papers from 2018. She noted at the start of her talk that while this is a surgical audience, all of the studies were from the medial oncology literature. This comment highlighted the multidisciplinary nature of breast cancer care – the entire treatment team needs to be aware of the latest advances and updates.

The TAILORx study assessed Oncotype Dx results and noted that many patients previously classified as intermediate risk could now be classified as low risk. Therefore, a larger percentage of patients do not need chemotherapy. However, questions remain for patients under the age of 50.

The TEXT / SOFT trials evaluated the use of ovarian suppression in premenopausal women with hormone receptor positive breast cancer. Ovarian suppression resulted in improved disease free and overall survival, but the magnitude of improvement varied according to recurrence risk. High risk patients may have 10-15% improvement. However, quality of life and fertility may be impacted by ovarian suppression in these younger women

The KATHERINE study assessed the use of TDM1 in patients with Her2/neu over-expressed tumors who did not exhibit a pathologic complete response (pCR) after neoadjuvant (before surgery) chemotherapy. Those who received adjuvant TDM1 versus trastuzumab showed an improved disease free survival, but more study is needed to assess the effect on overall survival.

Dr. V. Craig Jordan delivered the American Cancer Society / SSO Basic Science Lecture: The SERM Saga: Something From Nothing. Dr. Jordan’s presentation was a nice history lesson about the discovery and use of tamoxifen as a treatment for breast cancer.
– Dr. Jordan noted the early clues that endocrine therapy might be effective for some breast cancers – removal of the ovaries, adrenal glands, and even part of the pituitary gland led to improved outcomes (with a fair amount of associated risk)
– Tamoxifen was initially developed as a contraceptive agent, but it was not successful and was going to be discarded by the manufacturer
– The link to endometrial cancer and tamoxifen was initially denied, despite some interesting studies by Dr. Jordon noting the association. He noted that the early studies evaluating tamoxifen simply did not assess for endometrial cancer
– He noted that the cumulative frequency of uterine cancer with 2 years of tamoxifen is ~1.5%, and with 5 years of tamoxifen ~5.5%. He commented that if the studies were performed today, the data monitoring committees would “go apoplectic” over these results
– Raloxifene in early studies showed decrease in breast cancer but also decrease in bone fractures – this led to the STAR trial which assessed the ability of raloxifene and tamoxifen to reduce breast cancer development in high-risk women
– He discussed other drugs, derived from tamoxifen, that are being developed – searching for those with improved side effect profiles
– He quoted George S. Patton: “If everyone is thinking alike, then someone isn’t thinking”

Presidential Address – Serendipity and Strategy on the Path of Progress
Dr. Armando Giuliano, known to some as the “father” of the sentinel node biopsy, provided some interesting details on how his research process unfolded. He noted that “my success has been due to good luck, mixed with hard work, strategic planning, and serendipity.” Like those before him who proposed less aggressive surgical therapy for breast cancer, he was met with a fair amount of criticism. Patients and surgeons have benefited from his perseverance and dedication.

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 have not been subject to the peer-review process, and may represent incomplete data.

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

This post has not been endorsed by the Society of Surgical Oncology.

 

9 November 2015

The American Society of Breast Surgeons Foundation has just launched a patient information website – Breast360.org. The site was developed by breast surgeons, and patient advocates have had input and oversight during the entire process. Please take a look, and feel free to provide feedback if you have a suggestion for additional content.