Commentary

Studies review updates in mammography, mastectomy and margin width

Three studies presented at the American Society of Breast Surgeons Annual Meeting provide new data on relevant topics in the field of breast cancer treatment and prevention. These matters — which include mammography screening for women outside the age parameter of guidelines, increasing use of nipple-sparing mastectomy, and appropriate margin width for ductal carcinoma in situ (DCIS) — are important issues to address among clinicians and their patients.

Screening guidelines

The new mammography screening guidelines have caused significant angst for women and advocates who question why screening mammography is no longer being mandated to start at age 40 years. It is important to understand that these guidelines are for women at average risk.

Hughes and colleagues found that half of all women aged 40 to 44 years presenting to a large academic center were at increased risk, such that they may (a) qualify for earlier screening mammography, (b) have additional imaging, or (c) need genetic counseling (see related story). How well these data reflect the general population is unclear as this is a select group, but the message remains clear: Women need to know their risk.

Anees B. Chagpar

The models used in the Hughes study often are not readily accessible to clinicians functioning outside a high-risk clinic. Therefore, there is a need for global education of women and their primary care physicians to understand when they ought to seek a more formal risk assessment. Certainly, a family history is a key risk factor, but other factors — such as a previous history of atypia, lobular carcinoma in situ and radiation therapy to the chest — would all put women at increased risk, regardless of their family history. Knowing your risk is critical to determine whether the guidelines are applicable to you.

Nipple-sparing mastectomies

The work by Jakub and colleagues adds to our growing body of data that nipple-sparing mastectomies are safe in BRCA–mutation carriers (see related story). As women are becoming increasingly aware of their genetic risk, and genetic counselors are finding more mutations that put patients at increased risk, more patients are opting for this cosmetically appealing approach to reduce their risk for developing breast cancer.

In their study, Jakub and colleagues found that no patients developed breast cancer in 34 months of follow-up. Seven patients died of breast cancer during the follow-up period, but these were all patients who either had a previous or coexisting malignancy, and their deaths were attributed to that. No cancer was found in the mastectomy skin flap or nipple of the prophylactic mastectomy.

Although these data suggest that nipple-sparing mastectomy is safe as a prophylactic option, it should be noted that they excluded patients who were found to have occult malignancy in the prophylactic mastectomy and those with variants of unknown significance. It would have been interesting to see whether the results would have been significantly different if these patients were included. One would surmise that, because the majority of variants of unknown significance turn out to be benign, this would only confirm nipple-sparing mastectomies to be safe in this population.

Further, although the deaths were in patients who had previous disease, one would think that if disease was occult, it was likely of low volume and less likely to metastasize. Although these assumptions cannot be validated in the current study, they would make sense in light of the body of literature that exists in this arena.

DCIS margins

The study by Khan and colleagues reopens the age-old debate about the nature of DCIS margins, and whether this disease entity is overtreated. Their work highlights the fact that DCIS is not a singular entity, but rather a heterogeneous spectrum of disease, and although there may be some who feel that low-grade DCIS is overtreated, DCIS is not uniformly a benign entity.

Two main points become clear in this work: Both biology and treatment matter. Regardless of margin width, high-grade DCIS has nearly a threefold higher chance of local recurrence at 5 years than low- to intermediate-grade disease (55% vs. 18% for < 1 mm margins; 23% vs. 8% for 1 mm margins).

Further, margins matter. Regardless of grade, margins larger than 1 mm are associated with half the chance of local recurrence at 5 years than narrower margins (8% vs. 18% for low to intermediate grade; 23% vs. 55% for high grade).

In the SHAVE trial — published last year in The New England Journal of Medicine — we found that extent of DCIS was an independent predictor of positive margins. Hence, patients with extensive high-grade DCIS may be more predisposed to having positive margins, and may be at higher risk for local recurrence.

Given that roughly half of local recurrences of DCIS present with invasive disease, it is critical that we do not minimize the risk for this disease. DCIS is not always indolent, curable and overtreated; indeed, it can be a virulent precursor of recurrence that should not be underestimated, particularly in patients with extensive high-grade disease in whom wider margins cannot be obtained.

Reference:

Chagpar AB, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1504473.

For more information:

Anees B. Chagpar, MD, MSc, MBA, MA, MPH, FACS, FRCS(C), is associate professor of surgery (oncology), director of The Breast Center at Smilow Cancer Hospital at Yale-New Haven and assistant director of global oncology at Yale Comprehensive Cancer Center. She can be reached at anees.chagpar@yale.edu.

Disclosure: Chagpar reports no relevant financial disclosures.

Three studies presented at the American Society of Breast Surgeons Annual Meeting provide new data on relevant topics in the field of breast cancer treatment and prevention. These matters — which include mammography screening for women outside the age parameter of guidelines, increasing use of nipple-sparing mastectomy, and appropriate margin width for ductal carcinoma in situ (DCIS) — are important issues to address among clinicians and their patients.

Screening guidelines

The new mammography screening guidelines have caused significant angst for women and advocates who question why screening mammography is no longer being mandated to start at age 40 years. It is important to understand that these guidelines are for women at average risk.

Hughes and colleagues found that half of all women aged 40 to 44 years presenting to a large academic center were at increased risk, such that they may (a) qualify for earlier screening mammography, (b) have additional imaging, or (c) need genetic counseling (see related story). How well these data reflect the general population is unclear as this is a select group, but the message remains clear: Women need to know their risk.

Anees B. Chagpar

The models used in the Hughes study often are not readily accessible to clinicians functioning outside a high-risk clinic. Therefore, there is a need for global education of women and their primary care physicians to understand when they ought to seek a more formal risk assessment. Certainly, a family history is a key risk factor, but other factors — such as a previous history of atypia, lobular carcinoma in situ and radiation therapy to the chest — would all put women at increased risk, regardless of their family history. Knowing your risk is critical to determine whether the guidelines are applicable to you.

Nipple-sparing mastectomies

The work by Jakub and colleagues adds to our growing body of data that nipple-sparing mastectomies are safe in BRCA–mutation carriers (see related story). As women are becoming increasingly aware of their genetic risk, and genetic counselors are finding more mutations that put patients at increased risk, more patients are opting for this cosmetically appealing approach to reduce their risk for developing breast cancer.

In their study, Jakub and colleagues found that no patients developed breast cancer in 34 months of follow-up. Seven patients died of breast cancer during the follow-up period, but these were all patients who either had a previous or coexisting malignancy, and their deaths were attributed to that. No cancer was found in the mastectomy skin flap or nipple of the prophylactic mastectomy.

Although these data suggest that nipple-sparing mastectomy is safe as a prophylactic option, it should be noted that they excluded patients who were found to have occult malignancy in the prophylactic mastectomy and those with variants of unknown significance. It would have been interesting to see whether the results would have been significantly different if these patients were included. One would surmise that, because the majority of variants of unknown significance turn out to be benign, this would only confirm nipple-sparing mastectomies to be safe in this population.

Further, although the deaths were in patients who had previous disease, one would think that if disease was occult, it was likely of low volume and less likely to metastasize. Although these assumptions cannot be validated in the current study, they would make sense in light of the body of literature that exists in this arena.

DCIS margins

The study by Khan and colleagues reopens the age-old debate about the nature of DCIS margins, and whether this disease entity is overtreated. Their work highlights the fact that DCIS is not a singular entity, but rather a heterogeneous spectrum of disease, and although there may be some who feel that low-grade DCIS is overtreated, DCIS is not uniformly a benign entity.

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Two main points become clear in this work: Both biology and treatment matter. Regardless of margin width, high-grade DCIS has nearly a threefold higher chance of local recurrence at 5 years than low- to intermediate-grade disease (55% vs. 18% for < 1 mm margins; 23% vs. 8% for 1 mm margins).

Further, margins matter. Regardless of grade, margins larger than 1 mm are associated with half the chance of local recurrence at 5 years than narrower margins (8% vs. 18% for low to intermediate grade; 23% vs. 55% for high grade).

In the SHAVE trial — published last year in The New England Journal of Medicine — we found that extent of DCIS was an independent predictor of positive margins. Hence, patients with extensive high-grade DCIS may be more predisposed to having positive margins, and may be at higher risk for local recurrence.

Given that roughly half of local recurrences of DCIS present with invasive disease, it is critical that we do not minimize the risk for this disease. DCIS is not always indolent, curable and overtreated; indeed, it can be a virulent precursor of recurrence that should not be underestimated, particularly in patients with extensive high-grade disease in whom wider margins cannot be obtained.

Reference:

Chagpar AB, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1504473.

For more information:

Anees B. Chagpar, MD, MSc, MBA, MA, MPH, FACS, FRCS(C), is associate professor of surgery (oncology), director of The Breast Center at Smilow Cancer Hospital at Yale-New Haven and assistant director of global oncology at Yale Comprehensive Cancer Center. She can be reached at anees.chagpar@yale.edu.

Disclosure: Chagpar reports no relevant financial disclosures.