29 December 2020

Anxiety related to the possibility of cancer recurrence is common among those who have been treated for cancer. However, less common is the awareness that an entirely different cancer may develop, known as a second primary cancer (SPC). Reasons for second primary cancer include general risk factors such as aging (a risk factor for many cancers), lifestyle factors that may have contributed to the initial cancer such as smoking, alcohol intake and obesity, and genetic factors including known deleterious genetic variants (such as BRCA 1 or 2) or links between cancers even in the absence of a known mutation (breast cancer survivors are at increased risk for colon cancer).

In a study recently published in the Journal of the American Medical Association*, researchers used the SEER database and evaluated data from patients diagnosed with cancer between 1992 – 2011. They evaluated those who survived at least 5 years from their initial diagnosis. Among 1.54 million, the most common first primary cancers (FPC) were breast in women and prostate in men. For the entire cohort, approximately 10% developed a SPC. The risk of developing and dying from a SPC was greater than expected compared with the general population for 18 and 27 of the 30 FPC respectively among men and 21 and 28 of the 31 FPC among women.

Second primary cancer likelihood depended on type of primary cancer. However, as this was a retrospective database review, the researchers were not able to take into account initial treatment such as radiation or chemotherapy, that could influence the development of a new cancer. They found that cancers associated with smoking or obesity accounted for “substantial portions” of SPC incidence and deaths. These cancers included lung, bladder, oral / throat, colorectal, pancreatic, uterine (endometrial) and liver cancers.

In an accompanying editorial*, Ganz and Casillas noted that primary care providers and patients need to be aware of the possibility of second primary cancers. Relevant screenings should be ordered, and they noted that patients who had received both chemotherapy and radiation are well known to be at elevated risk for SPC. They also stressed that special attention should be paid to survivors of young adult cancers, and physicians need to be aware of their prior treatments and whether those treatments may convey an increased risk for SPC (such as radiation for Hodgkin’s lymphoma increasing subsequent breast cancer risk.

Ganz and Casillas commented that continued attention needs to be paid to the lifestyle factors that can influence cancer development including alcohol, tobacco and obesity. They noted that many FPC and SPC  related to tobacco are due to prior exposures, but there remain opportunities to reduce continued and future use, which could impact SPC risk especially among young adult cancer survivors. 

Perez et al, in a separate editorial*, proposed a more comprehensive approach to address  tobacco use and obesity including better and more widespread access to education, addiction management and obesity treatment programs. They also stressed that as some cancer treatments are carcinogenic, it is important to avoid imaging tests and some types of cancer treatments when not necessary or when less toxic alternatives exist. They concluded by stating that “A combination of less carcinogenic oncologic therapies and healthier lifestyles may help us protect future cancer survivors from facing cancer yet again.”

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

10 October 2020

Breast implants that are used for reconstruction or cosmetic augmentation can have either a smooth or textured surface, and plastic and reconstructive surgeons may prefer one or the other type of implant for various reasons. Last year, the US FDA recalled several types of textured implants manufactured by Allergan due to their link to breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). BIA-ALCL is not thought to be associated with an increased risk of breast cancer, and is generally treated by removal of the implant and associated fibrous capsule (more information on BIA-ALCL and the FDA recall here).

A study recently published in JAMA Surgery* found that women who underwent post-mastectomy reconstruction using textured implants had a higher rate of breast cancer recurrence compared with those who had reconstruction performed with smooth implants.

The retrospective study was performed in South Korea, and evaluated the outcomes of 650 women (total of 687 implants) who underwent mastectomy and implant reconstruction for breast cancer, from 2011 – 2016. 413 of the implants were textured and 274 were smooth. Mean age was 43.5 and the majority of patients had early stage (I or II) breast cancer. 15% received postoperative radiation therapy and 44% received postoperative chemotherapy.

There were 28 breast cancer recurrences over the study period (4%). Local recurrences (in the chest wall area) were the same in both groups. 10 patients experienced distant recurrence (metastatic disease), and all had received textured implants. 

One cannot conclude from this study that the breast cancer recurrence was due to the textured implants, and limitations of the work include the retrospective nature. Larger, multi-institution studies are likely. In the meantime, it is reasonable for patients who are planning on implant reconstruction to discuss implant type, associated risks, and alternatives with their plastic surgeon.

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

24 December 2019 (updated 6 February 2020)

recently published study evaluated the association between hair products and breast cancer risk.

The researchers surveyed women enrolled in the Sister Study – these women had a sister with a history of breast cancer but had not been diagnosed themselves. The study group included over 46,000 women, ages 35-74, enrolled between 2003 – 2009. Study participants were asked at enrollment about their history and frequency of hair product use (permanent dye, semi-permanent dye, and straighteners) within the previous 12 months. Mean follow up was 8.3 years, and 2794 participants were diagnosed with breast cancer during that time (5.9%).

The main findings included:

  • 55% of participants used permanent hair dye at the time of enrollment
  • Use of permanent hair dye was associated with a 45% increased risk of breast cancer in black women and a 7% increased risk in white women [Note – only 11.5% of the patients in the no-dye and 6.6% of patients in the permanent dye groups were Black]
  • Risk of breast cancer increased with increased frequency of permanent dye use
  • 9.9% of participants used hair straightening products, and use was associated with an 18% increased risk of breast cancer
  • Risk of breast cancer increased with increased frequency of hair straightener use
  • Nonprofessional application of dyes and straighteners to others was associated with increased breast cancer risk
  • There was no association between the use of semi-permanent hair dyes and breast cancer

It is known that hair dyes and chemical straighteners contain some compounds which have estrogen-like activity, and some of the chemicals are known to cause cancer in animals, but studies in women have been inconsistent. As this was an observational study, a direct cause-and-effect relationship cannot be determined based on the results. All women in the study were at increased risk of developing breast cancer due to their family history, and many other risk factors, as well as details regarding specific hair product use, cannot be accounted for. In addition, the authors reported on relative risk, but did not document absolute increases in risk, and not all of the associations were statistically significant. The authors concluded that the results “provide evidence to support the relationship of hair dye and straightener use with breast cancer risk and highlight potential differences in associations by ethnicity.”

In his blog post reviewing this study, epidemiologist Gideon M-K noted that “While the headlines only reported the 45% increase that seemed the scariest, the absolute increase in risk was only about 0.05%. To put it another way, for every 10,000 women who never dye their hair, about 72 get breast cancer every year. For women who dye their hair every month, this rate goes up to about 77 in 10,000.”

Some may feel more comfortable controlling what they can, and therefore will decide to avoid the use of these products. However, just like many other studies that show associations between foods, chemicals, behaviors and cancer development, this study is far from conclusive.

ASCO Post: Study suggests association between increased risk of breast cancer and use of chemical hair products

FORCE XRAY: Do Hair Dyes and Straighteners Increase Breast Cancer Risk?

NY Times: Hair dyes and straighteners may raise breast cancer risk for black women

Washington Post: Hair dye raises questions about chemicals’ effect, changing trends

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

13 December 2019

For women at high risk for breast cancer, tamoxifen and raloxifene have both been shown to be effective in reducing risk by approximately 30-40%. A recent small study found that low dose (5mg) of tamoxifen is also effective for risk reduction.

In post-menopausal women with a history of breast cancer, it is known that anastrozole (Arimidex), an aromatase inhibitor, is more effective than tamoxifen in terms of reducing breast cancer recurrence. Anastrozole can also be used in high risk women to decrease the likelihood of breast cancer developing, but there is not as much data as we have for tamoxifen.

Updated results of the International Breast Cancer Intervention Study II (IBIS II)* were presented at the San Antonio Breast Cancer Symposium and published in The Lancet. This study compared 5 years of anastrozole versus placebo in post-menopausal women who were at elevated risk for breast cancer. 3864 women were included. After median follow up of 10.9 years, there were 85 breast cancer cases in the anastrozole group versus 165 in the placebo group, a 49% reduction. The “number (of patients) needed to treat” to prevent one breast cancer is 29. There were no differences in deaths. Interestingly, there was also a significant decrease in non-breast cancers in the anastrozole group (147 vs 200), primarily non-melanoma skin cancers. There was no increase in fractures or cardiovascular disease in patients taking anastrozole compared with placebo.

This study shows that as is the case for treatment of breast cancer in post-menopausal women, anastrozole is more effective than tamoxifen for risk reduction. However, side effects of anastrozole are well known (most commonly hot flashes, vaginal dryness, bone / joint pains, and osteoporosis), and may prevent some women from starting or completing a 5-year course of risk-reducing treatment. Women who are at high risk for breast cancer should also be aware of the increased screening (MRI in addition to mammogram) that is often recommended, and all women should understand the influence of lifestyle factors on breast cancer risk, including regular exercise, moderation in alcohol intake, following a healthy diet, and maintenance of an ideal body weight.

ASCO Post: Dr. Jack Cuzick IBIS II 10-year results

Risk Reducing Medications

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

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:

6 October 2019

The headline was promising: “Breast Cancer Awareness Month: 3 Ways to Prevent and Detect the Disease” – but the word “prevent” always gets my attention. Can we really prevent breast cancer?

As always, the context is important. When we look at populations, large groups of individuals, there is no question that a healthy diet, regular exercise, and limitations in alcohol intake will result in reduced rates of breast cancer (and other disease) development. So for populations, yes, we can prevent disease. Unfortunately it’s not that simple when it comes down to the individual level. Cancer, even breast cancer, is not one disease. People are complex and there are multiple factors influencing the likelihood of disease development in any one individual. For example, breast feeding lowers risk, but a woman who breast-fed her children is not immune from developing breast cancer. On an individual level, the best we have is risk reduction.

What’s the harm in using the term prevention when discussing risk factors at an individual level? It is not uncommon for a patient newly diagnosed with breast cancer to start second-guessing all of her life choices, and feeling guilty that she caused her disease:

The reality is that one can do everything “right” and still develop breast cancer and one can have a high alcohol intake and junk-food diet and never develop the disease. In the majority of individuals, we cannot determine exactly why breast cancer develops. We are all looking for answers and for control. Adopting a healthier lifestyle with known risk factors in mind will help contribute to a longer and healthier life. But there are no guarantees. Life is for living, and it’s too short to be burdened with guilt if disease does develop.

6 September 2019


The US Preventative Services Task Force (USPSTF) and the American Society of Clinical Oncology (ASCO) have both released updated recommendations on the use of medications (tamoxifen, raloxifene, anastrozole and exemestane) to reduce the risk of estrogen-receptor positive breast cancer in women who are considered to be at high risk for the disease. The use of these medications to reduce breast cancer risk is commonly known as “chemoprevention.” Tamoxifen, anastrozole and exemestane are also used in the treatment of estrogen receptor positive breast cancer. Summaries of the statements and links to the manuscripts and associated publications are provided at the end of this post.

Risk assessment may be performed using a variety of online calculators that take into account age, menstrual and pregnancy history, family history and prior breast biopsies – especially biopsies that show atypical hyperplasia or lobular carcinoma in situ (LCIS). Some models also take into account body mass index and breast density. These models tend to perform well in populations of women, but are not as accurate as predicting the likelihood of breast cancer development in an individual woman. The models calculate 5-year and lifetime breast cancer risks. The “average” woman has a 5-year risk of approximately 1% and lifetime risk of approximately 10-12%. The early studies evaluating risk-reducing medications considered a 5-year risk of 1.66% or greater as “high risk” (lifetime risk over 20% is also considered “high risk”). Both the USPSTF and ASCO statements focus on women age 35 and older with a 5-year risk of 3% or higher

The USPSTF and ASCO recommendations are similar. For women at high risk of developing breast cancer (3% or greater 5-year calculated risk OR high risk due to combination of factors – see below), it is recommended that patients consider the use of a risk-reducing medication, taking into account side effects of the medications and an individual patient’s medical condition and preferences. Both guidelines specifically do NOT recommend the use of risk-reducing medications in women who are not at elevated risk for the development of breast cancer. 

The risk factor combinations that convey increased risk and should prompt consideration of risk-reducing medications include:

From the USPSTF Statement:

  • Age 65 or older with one 1st degree relative with breast cancer
  • Age 45 or older with more than one 1st degree relative with breast cancer or one 1st degree relative who developed breast cancer before age 50
  • Age 40 or older with atypical hyperplasia or lobular carcinoma in-situ, or with a 1st degree relative with bilateral breast cancer 

From the ASCO Statement:

  • 1st degree relative with breast cancer diagnosed before age 45
  • Two 1st degree relatives with breast cancer diagnosed at any age
  • A 1st and 2nd degree relative with breast cancer

The USPSTF statement acknowledges that women with BRCA mutations and those who have received chest wall radiation at a young age are at increased risk, but it was felt that there was insufficient evidence to recommend chemoprevention in these patients. These women are included in the ASCO statement in the Clinical Considerations section of the manuscript.

Risk assessment and the decision to use risk-reducing medications is a challenging and at times confusing topic. Many studies report that the use of risk-reducing medications in high risk women can result in a 50% or greater reduction in the likelihood of developing invasive breast cancer compared with placebo. However, as the JAMA editorial by Drs. Pace and Keating notes, the absolute reduction in risk for an individual woman could be very low – less than 1 percentage point. They noted that over 100 high-risk women would need to be treated to prevent one breast cancer. Obviously when multiplied by the large number of women that might be impacted by these guidelines (noted to be approximately 10 million women in the US in the JAMA editorial by Drs. Daly and Ross) there is the potential to make a significant impact on the incidence of breast cancer. None of these medications have been shown to improve breast cancer-related survival rates in high-risk women. 

Many of the early studies that determined the effectiveness of these medications in reducing risk defined “high risk” as a 1.66% or greater 5-year risk. However, both USPSTF and ASCO recommend using the 3% or greater level of 5-year risk as it was felt that these women at the highest level of risk are most likely to benefit from the medications, and that this benefit will be more likely to outweigh potential harms. But even these women may be more likely to NOT develop breast cancer.

In deciding on a medication, tamoxifen may be used in pre- or post-menopausal women. Raloxifene, anastrozole and exemestane are only for use in post-menopausal women.

Both statements acknowledge the potential side effects that may occur with use of these medications. Some of the more common potential side effects include uterine cancer (tamoxifen), blood clots (tamoxifen and raloxifene), bone / joint / muscle pains and bone loss (anastrozole and exemestane) and hot flashes (all medications). Generally, risk-reducing medications are used for 5 years although raloxifene may be used for longer periods of time as it is often used as a treatment for osteoporosis. The risk reduction appears to last approximately 8-10 years after the medication is stopped, and many studies report that side effects tend to improve shortly after medications are discontinued. The ASCO statement notes that 3 years of risk-reducing therapy may be effective. The paper also discusses a recent study that evaluated the use of low dose (5 mg as opposed to the usual 20mg)  tamoxifen versus placebo in high risk women. There was an approximately 50% reduction in the risk of invasive breast cancer among patients who took the low dose of tamoxifen – similar risk reduction to what is seen with the full 20mg dose.

Both statements mentioned other ways that risk can be reduced, including adoption of a healthy lifestyle (exercise, alcohol limitation, and weight management). Challenges in the use of risk assessment models and in discussing risk reducing medications include limited time and lack of patient decision aids. More data is needed on the risks and benefits of the medications in some patient populations. 

It is hoped that ongoing research evaluating the use of polygenic risk scores (a form of genetic testing) will add more insight to an individual’s level of risk in the (hopefully) near future. Drs. Daly and Ross noted in their editorial that “In the new era of precision medicine, there is a realization that one size fits all is no longer acceptable for most treatments.” and that “More efficient and sophisticated tools to more precisely quantify each individual’s benefit / risk for a variety of chemoprevention drugs may ultimately translate into precision medicine for breast cancer prevention.” Physicians and patients will certainly welcome more precise, tailored information to help guide the decision-making process for women who are at high risk for breast cancer.

USPSTF Recommendation: Medications to Reduce the Risk of Breast Cancer
ASCO Guideline Update: Use of Endocrine Therapy for Breast Cancer Risk Reduction

If access to any of the references articles is desired, please email me:  contact at drattai dot com and I will be happy to provide a copy.

23 August 2019

Earlier this week, the United States Preventative Services Task Force (USPSTF) released an updated recommendation for genetic testing for BRCA 1 and 2 mutations. Their previous guideline, released in 2013, recommended risk assessment and consideration of testing in women with a family history of breast and/or ovarian cancer. The current guidelines add consideration for ancestry and personal history of breast, ovarian, fallopian tube or peritoneal cancer (BRCA-associated cancers for the purpose of this post). Under the Affordable Care Act, private insurers follow USPSTF recommendations, often with no out-of-pocket cost to the patient.

The BRCA 1 and 2 genes are involved in DNA repair. Mutations in these genes may impact the ability of a cell to repair DNA damage resulting in an increased risk of certain cancers. In women, the most common BRCA-associated cancers are breast and ovarian cancer. In men, the most common BRCA-associated cancers are prostate, breast and pancreatic cancers as well as melanoma. The abnormal genes can be inherited from the mother or father.  Mutations in BRCA 1 and 2 genes have been identified in every racial and ethnic group with a prevalence ranging from 1 in 40 to 1 in 500. The Ashkenazi Jewish population has the highest mutation prevalence.  Not everyone that inherits an abnormal gene will develop the cancer – the risk and type of cancer depend on the specific mutation and many other factors. Mutations in the BRCA genes account for approximately 5-10% of breast cancers and approximately 15% of ovarian cancers.

The updated USPSTF recommendation applies only to women (they did not address genetic testing in men) and only applies to the BRCA 1 and 2 genes, which are the most common genes associated with hereditary breast and ovarian cancer. 

The current guideline recommends a 3-step process. In patients who have a personal or family history of BRCA-associated cancers or a hereditary susceptibility (Ashkenazi Jewish) the task force recommends:

  • Use of a validated tool to determine likelihood of a genetic mutation
  • Referral of patients with a high likelihood of carrying a genetic mutation for genetic counseling
  • Genetic testing if the results would impact medical decision making

It is important to note that they are not stating that all Ashkenazi Jewish women, or that all women with a personal or family history of breast or ovarian cancer be tested – but that they be evaluated and then considered for testing based on likelihood of having a deleterious (harmful) mutation. They recommend against risk assessment, genetic counseling and genetic testing in those with a personal or family history of cancer or ancestry not associated with a high likelihood of deleterious BRCA mutations. 

Identification of patients who carry mutations in these genes is important for several reasons. In those who do not have cancer, identification of a mutation carrier may lead to recommendations for more intensive screening (most commonly annual MRI in addition to annual mammography for breast cancer surveillance) or prophylactic surgery. Family members can also be appropriately counseled and tested. Tamoxifen may be considered for breast cancer risk reduction. However, in an accompanying editorial, Dr. Lisa Newman noted that breast cancers that develop in women with BRCA 1 mutations are more likely to be “triple negative”, which are not responsive to tamoxifen or other therapies that target the estrogen receptor. BRCA 2 related breast cancers are more often estrogen receptor positive, and tamoxifen may be an option in these patients for risk reduction.

In patients that have a history of a BRCA-associated cancer, knowledge of genetic status can inform surveillance recommendations for other associated cancers as well as counseling and testing of family members. 

The USPSTF specified that patients with a prior history of BRCA-associated cancers, who “have completed treatment are considered cancer-free but have not been previously tested” are included in this guideline. I believe it is unfortunate that they did not include newly diagnosed patients in this guideline as knowledge of mutation status can influence surgical recommendations and may influence systemic therapy (chemotherapy) recommendations, a point made in the editorial by Drs. Sharon Domchek and Mark Robson. There may also be value in testing patients who have metastatic disease as their family members can then make informed decisions regarding their own health. The most recent American Society of Breast Surgeons genetic testing guideline recommends that all breast cancer patients be considered for genetic testing.

The USPSTF recommendations did not touch on this, but It is important to note that if BRCA testing was performed prior to 2012-2014, consideration should be given to repeat testing. A large number of mutations have been identified since that time, and some who have previously testing negative may actually carry a deleterious mutation.

Genetic testing in men was not addressed in the current USPSTF statement. Drs. Rachel Yung and Larissa Korde, in an accompanying editorial, stated that lack of inclusion of men in the guideline was a “missed opportunity”. They noted that that metastatic prostate cancer is the most common BRCA-associated cancer in men and that the National Comprehensive Cancer Network (NCCN) guidelines list family history of metastatic prostate cancer is an indication for genetic counseling and BRCA testing. Many patients (and some physicians) are unaware that BRCA mutations can be inherited from male relatives and may lead to cancer development in men. For that reason, some have called for the renaming of “Hereditary Breast and Ovarian Cancer Syndrome” to “King Syndrome”, after Dr. Mary-Claire King, the scientist who discovered the location of the BRCA 1 gene and its relationship to hereditary breast and ovarian cancer.

In addition, not specifically covered in this statement, but discussed in editorials by Dr. Lisa Newman, Drs. Susan Domchek and Mark Robson, and Dr. Padma Sheila Rajagopal et al was racial and socioeconomic disparities in genetic testing and the importance of ongoing work in this area.

While (in my opinion) the current recommendations are incomplete, they are a step forward in helping to ensure patients with deleterious mutations, and their family members, are properly identified and counseled regarding their risk and their options. 

Men and women should be aware of their family history of all cancers (going back 3 generations), not just breast and ovarian cancer. Those who feel they fit the new guidelines based on family history, personal history, or ethnic background, even if previously tested (before 2012-2014) should speak with their physician about referral to a provider who specializes in cancer genetics for consideration of testing. 

If access to any of the references articles is desired, please email me: contact at drattai dot com and I will be happy to provide a copy.

References and Resources:

8 July 2019

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

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

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

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

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

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

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

5 July 2019

A study recently published in The Lancet Oncology found that the addition of MRI to mammography screening in high-risk patients detected breast cancers in earlier stages, but found that this technology was associated with a higher likelihood of false-positive results.

The study was performed at 12 hospitals in the Netherlands. Patients who were age 30-55 with a lifetime risk of breast cancer greater than 20% due to family history, but who tested negative for deleterious mutations in BRCA 1/2 and TP53 genes, were eligible to participate. Patients were randomized to one of the following surveillance arms:

  • Annual MRI, annual clinical breast exam, every other year mammogram [MRI-MG], or
  • Annual mammogram and annual clinical breast exam [MG]

1355 women were randomized and 231 were registered – the patients who were registered were those who did not provide consent for randomization, but followed one or the other protocol. Results from the patients who were registered but not randomized were used only in a portion of the data analysis.  

The authors found that over the 7-year study period:

  • 40 breast cancers were detected in the MRI-MG group, 15 were detected in the MG group
  • 24 invasive breast cancers were detected in the MRI-MG group, 8 were detected in the MG group
  • Invasive breast cancers detected in the MRI-MG group were smaller (9 versus 17 millimeters) than those in the MG group
  • Lymph node involvement was less likely to be seen in the MRI-MG group (4 of 24 cases, 17%) versus the MG group (5 of 8 cases, 63%)
  • There was one interval cancer (detected between screening exams) in the MRI-MG group and 2 in the MG group
  • Increased breast density was associated with higher stage at diagnosis in both study groups
  • Clinical breast exams generated a large number of false-positive results in both groups and detected only one cancer.

This study adds to the evidence nothing that the addition of MRI to screening mammography will increase the rate of cancer detection. National guidelines in the US do recommend breast MRI on an annual basis, in addition to annual mammography, for patients with a lifetime risk of 20% or greater. This study was not designed to assess outcomes for the patients who were diagnosed with breast cancer, but the authors postulated that MRI screening might lead to mortality reduction due to earlier stage at diagnosis. As reduction in mortality is the goal of screening, they stated that they plan to link the current study results with their national cancer database, and eventually publish 10-year mortality statistics for each of the groups. 

Additional Information: ASCO Post