Marie Catherine Lee

Male Breast Cancer: Management and Follow‐up Recommendations

Abstract:  National Comprehensive Cancer Network (NCCN) guidelines for female breast cancer treatment and surveillance are well established, but similar guidelines on male breast cancers are less recognized. As an NCCN institution, our objective was to examine practice patterns and follow‐up for male breast cancer compared to established guidelines for female patients. After Institutional Review Board approval, a prospective breast database from 1990 to 2009 was queried for male patients. Medical records were examined for clinico‐pathological factors and follow‐up. The 5‐year survival rates with 95% confidence intervals were estimated using Kaplan–Meier method and Greenwood formula. Of the 19,084 patients in the database, 73 (0.4%) were male patients; 62 had complete data. One patient had bilateral synchronous breast cancer. The median age was 68.8 years (range 29–85 years). The mean/median invasive tumor size was 2.2/1.6 cm (range 0.0–10.0 cm). All cases had mastectomy (29 with axillary node dissection, 23 with sentinel lymph node biopsy only, 11 with sentinel node biopsy followed by completion axillary dissection). Lymph node involvement occurred in 25/63 (39.7%). Based on NCCN guidelines, chemotherapy, hormonal therapy, and radiation are indicated in 34 cases, 62 cases, and 14 cases, respectively. Only 20/34 (59%) received chemotherapy, 51/62 (82%) received hormonal therapy, and 10/14 (71%) received post‐mastectomy radiation. Median follow‐up was 26.2 months (range: 1.6–230.9 months). The 5‐year survival estimates for node positive and negative diseases were 68.5% and 87.5%, respectively (p = 0.3). Despite the rarity of male breast cancer, treatment options based on current female breast tumors produce comparable results to female breast cancer. Increased awareness and a national registry for patients could help improve outcomes and tailor treatment recommendations to the male variant.

Acceptance and adherence to chemoprevention among women at increased risk of breast cancer

BACKGROUND Chemoprevention is an option for women who are at increased risk of breast cancer (five year risk ≥1.7%). It is uncertain, however, how often women accept and complete five years of therapy and whether clinical or demographic factors predict completion. METHODS Medical records were abstracted for 219 women whose five year risk of breast cancer was ≥1.7% and who were offered chemoprevention while attending a high risk breast clinic at the Moffitt Cancer Center. We examined the likelihood of accepting chemoprevention and completing five years of therapy, and potential clinical and demographic predictors of these outcomes, using multivariable logistic regression and survival analysis models. RESULTS There were 118/219 women (54.4%) who accepted a recommendation for chemoprevention and began therapy. The likelihood of accepting chemoprevention was associated with lifetime breast cancer risk and was higher for women with specific high risk conditions (lobular carcinoma in situ and atypical ductal hyperplasia). Women with osteoporosis and those that consumed alcohol were also more likely to accept medication. There were 58/118 (49.2%) women who stopped medication at least temporarily after starting therapy. Based on survival curves, an estimated 60% of women who begin chemoprevention will complete five years of therapy. CONCLUSIONS A substantial percentage of women at increased risk of breast cancer will decline chemoprevention and among those that accept therapy, approximately 40% will not be able to complete five years of therapy because of side effects.

Impact of axillary ultrasound (AUS) on axillary dissection in breast conserving surgery (BCS)

Preoperative axillary ultrasound (AUS) in clinically node‐negative patients may increase axillary lymph node dissection (ALND) in ACoSOG Z0011‐eligible patients. We hypothesize that AUS identifies operative axillary disease (>3 positive nodes) in women undergoing breast conserving surgery (BCS).

Breast cancer in young women: special considerations in multidisciplinary care

Breast cancer is one of the most prevalent cancers in females, and 5%–7% of breast cancer cases occur in women under 40 years of age. Breast cancer in the young has gained increased attention with an attempt to improve diagnosis and prognosis. Young patients tend to have different epidemiology, presenting with later stages and more aggressive phenotypes. Diagnostic imaging is also more difficult in this age group. Multidisciplinary care generally encompasses surgeons, medical oncologists, radiation oncologists, radiologists, and social workers. Other special considerations include reconstruction options, fertility, genetics, and psychosocial issues. These concerns enlarge the already diverse multidisciplinary team to incorporate new expertise, such as reproductive specialists and genetic counselors. This review encompasses an overview of the current multimodal treatment regimens and the unique challenges in treating this special population. Integration of diagnosis, treatment, and quality of life issues should be addressed and understood by each member in the interdisciplinary team in order to optimize outcomes.

The presence of extensive retraction clefts in invasive breast carcinomas correlates with lymphatic invasion and nodal metastasis and predicts poor outcome: a prospective validation study of 2742 consecutive cases.

We previously reported that the presence of extensive retraction clefts (RC) in breast cancers correlates with increasing tumor size and grade as well as lymphatic tumor spread and predicts poor outcome. This study is a prospective validation of our prior results. Consecutive cases of invasive breast carcinoma (n=2742) were reviewed to determine the diagnoses, including histologic type, grade, presence of lymphovascular invasion (LVI), and extent of RC. No differences were found in the extent of RC between corresponding core needle biopsy and surgical samples. Extent of RC showed a significant correlation with tumor size, grade, LVI, and nodal metastasis in both core needle biopsy and surgical specimens. These associations remained significant in subset analyses of small (⩽1 cm), node-negative and node-positive tumors. Extensive RC predicted poor recurrence-free (P<0.0001) and overall (P<0.0001) survival and remained significant in subset analyses of node-negative (P=0.0015 and 0.0021, respectively) and node-positive (P=0.0039 and 0.0214, respectively) cases. Carcinomas without LVI but extensive RC were associated with better outcome than carcinomas with LVI but worse than those without LVI and low RC. This prospective study confirms that the presence of extensive RC in invasive breast carcinomas correlates with aggressive tumor features and lymphatic tumor spread. Extensive RC appears to be an independent factor predictive of poor outcome in node-negative and node-positive disease. Our results support the hypothesis that RCs are the morphologic reflection of biological changes in tumor cells playing a role in lymphatic tumor spread and likely represent an early stage of LVI with similar clinical implications.

Ipsilateral nodal recurrence after axillary dissection for breast cancer

INTRODUCTION Level I/II axillary lymph node dissection (ALND) is the standard operation for patients with node-positive breast cancer. The objective of this study was to assess the incidence of regional nodal recurrence (RNR) after ALND performed for definitive operative treatment for primary breast cancer. MATERIALS AND METHODS A retrospective, Institutional Review Board-approved query of our single-institution National Comprehensive Cancer Network database was performed for patients undergoing ALND who developed subsequent RNR. All patients were treated from 1999 to 2009. A detailed chart review was performed and clinical, pathologic, treatment, and outcome data were collected. RESULTS A total of 1614 patients had an ALND for initial staging; 14/1614 (0.9%) patients had RNR. Two other patients had contralateral breast/axillary recurrences and were excluded. The mean age at diagnosis for the sample group was 52.7 y (range 34-77); mean follow-up time was 47.1 mo (range 12.6-114.6). The median number of nodes for ALND was 16 (range 8-27). The median number of positive nodes was 2.5 (range 0-7). Nine (64.3%) cases were estrogen receptor/progesterone receptor negative. Twelve (85.7%) patients had axillary recurrences, and six of 12 (50.0%) had concurrent chest wall lesions. Twelve patients (85.7%) had distant metastases; nine of 12 (75.0%) died; two were lost to follow-up. Mean time from RNR to distant recurrence was 6.0 mo (range 0-29.3 mo). CONCLUSIONS RNR after ALND is rare but a harbinger of poor outcome. This is apparent regardless of treatment used for initial disease or recurrence. Specifically, RNR after primary ALND is related to increased risk of mortality and distant metastatic disease.

Factors Affecting Lymph Node Yield in Patients Undergoing Axillary Node Dissection for Primary Breast Cancer: A Single-Institution Review

BackgroundA minimum of 10 level I/II axillary nodes is recommended for accurate breast cancer staging. The goal of this study was to assess the effect of neoadjuvant chemotherapy on lymph node yield at axillary lymph node dissection.MethodsA single-institution National Comprehensive Cancer Network (NCCN) breast cancer database was queried for cases with axillary node dissection from 2000 to 2008. All dissections were performed at the same institution. Demographic, chemotherapy, and clinicopathologic data were collected. Age and body mass index at diagnosis were calculated for subset analyses. Statistical analyses used Student’s t-test or analysis of variance with Tukey multiple comparison and Fisher’s exact test.ResultsTwo hundred forty patients had axillary node dissection after neoadjuvant chemotherapy; an additional 903 women with primary lymph node dissection were identified as contemporaneous control subjects. There was a far lower nodal yield in patients undergoing axillary dissection after neoadjuvant chemotherapy than those undergoing primary surgery. Patients with pathologic stage II or III disease undergoing primary surgery had more lymph nodes at axillary dissection than stage I disease.ConclusionsAge, type of breast surgery, body mass index, and clinical stage have no effect on yield of lymph nodes at axillary lymph node dissection. Neoadjuvant chemotherapy, however, is associated with a far fewer nodes at axillary dissection, and alteration of the guidelines should be considered for this population of patients.

Menopausal status does not predict Oncotype DX recurrence score

BACKGROUND Adjuvant treatment for early stage, estrogen receptor (ER) positive invasive breast cancer has been based on prognosticators such as menopausal status. The recurrence score (RS) from the 21-gene assay Oncotype DX (ODX) is predictive of a 10-y distant recurrence in this population but is rarely applied to premenopausal patients. The relationship between menopausal status and RS was evaluated. MATERIALS AND METHODS An institutional review board-approved retrospective review was conducted of invasive breast cancer patients with known RS. ODX eligibility was based on National Comprehensive Cancer Network guidelines or physician discretion. Perimenopausal women were classified as premenopausal for statistical analyses. Comparisons of menopausal status and RS were made using general linear regression model and the exact Wilcoxon rank-sum test. RESULTS Menopausal status was available for 575 patients (142 premenopausal, 433 postmenopausal). Median age was 46 y for premenopausal and 62 y for postmenopausal. Median invasive tumor size was 1.5 cm for both cohorts. Mastectomy rate was higher in the premenopausal group (54.8%) than postmenopausal (42%; P = 0.0001). Premenopausal women had a higher local-regional recurrence rate (2.8% versus 0%; P = 0.0384) but distant recurrence and overall survival were not statistically different (P = 0.6808). Median ER H-score was lower in premenopausal (H-score = 270) than postmenopausal women (H-score = 280; P < 0.0001). Median RS was 16 for both premenopausal (range, 0-54) and postmenopausal (range, 0-63) women. Menopausal status as a categorical variable was not predictive of RS (P-value = 0.6780). CONCLUSIONS Menopausal status has limited predictive power for distant recurrence. Therefore, menopausal status alone should not preclude performance of ODX in ER-positive, early stage breast cancer.

Recurrence Score across the age spectrum: Is there an age discrimination?

27 Background: Treatment planning for early-stage estrogen receptor (ER) positive, lymph node negative breast cancer was based on prognostic factors with limited predictive power such as age. The Recurrence Score (RS) from the Oncotype DX assay (ODX) provides predictive power transcending age but is rarely applied to the elderly or young patients (pts). We examined our experience with RS along the age continuum. METHODS Retrospective review was conducted of prospectively gathered breast cancer pts having a RS obtained as part of their cancer care. Eligibility for performance of the ODX was based on NCCN guidelines or physician discretion. Comparisons on RS were made by age groups (young: <45yrs; middle: >45yrs -<70yrs: elderly: >70yrs) using general linear regression model and the exact Wilcoxon Rank Sum Test. RESULTS 677pts had 681 tumors with RS available (89 young, 476 middle and 112 elderly pts). Median RS for the study pts was 17 (range 0-85) and 16, 17, and 15 for the young, middle, and elderly respectively. Median age was 58yrs (range: 27-95); young, middle, and elderly was 42, 58, and 74yrs respectively. Age as a continuous or categorical variable was not predictive of RS (p value = 0.38, 0.58 respectively). No significant differences were seen between age cohorts for histology, mitotic rate, lymphovascular invasion (LVI), grade, nodal status, stage, or strength of ER positivity. Mastectomy rates were higher in the young (57.5%), compared to the middle (42.5%) and elderly (39.6%) (p=0.02). Median invasive tumor size was 1.6, 1.5, and 1.5cm for young, middle, and elderly. Larger tumor size, as a continuous variable, equaled higher RS (p=0.046). Other significant factors predicting higher RS were increased mitosis (p<0.001), LVI (p=0.013), high grade (p<0.001), and weak (<10%) ER positivity (p<0.001). Nodal status, stage, and histology did not affect RS. CONCLUSIONS Age has limited predictive power for treatment planning for breast cancer. Age alone should not preclude recommendations for performance of ODX in estrogen receptor positive lymph node negative early stage breast cancer as the RS distribution across the spectrum of age is well matched.

The Pregnant Breast Cancer Patient: Are We Failing Our Most Vulnerable Population?

Breast cancer in the premenopausal population is uncommon, and breast cancer diagnosed in pregnancy is a frankly rare event, occurring in approximately 1/3,000 breast cancer cases annually. Considering the recent national and international trend of deferred childbearing, the incidence of breast cancer in pregnancy is likely to remain the same or increase in the coming years. Happily, breast cancer patients have been the beneficiaries of cutting edge cancer therapy in all modalities. These advances have not only significantly improved quality of life, they have also had a marked effect on the longevity of women diagnosed with breast cancer, even those presenting with late-stage disease. Thus, it is our responsibility as surgeons and oncologists to offer this special population the best that modern medicine has on hand. However, we frequently fall short of this goal when treating the pregnant breast cancer patient due to a lack of knowledge, the paucity of data, as well as fear for the potential current and future effects of therapy on the fetus. Although complicated by the timing of pregnancy, the data suggest that many of the surgical options recommended to non-pregnant patients should be considered for the gravid breast cancer patient, and termination of the pregnancy is by no means therapeutic. Given that the tumor biology seen in pregnant patients is similar to the nonpregnant premenopausal population, and that survival is dictated by tumor biology rather than the presence of a fetus, advocacy of the ‘therapeutic abortion’ is not only outdated but it borders on unethical. Unfortunately, the myth of the ‘therapeutic abortion’ continues to persist in the medical community, even to this day. For the newly-diagnosed pregnant patient, advances in breast imaging, particularly ultrasound, should not be forgotten. In particular, ultrasound of the axilla had demonstrated high sensitivity for axillary disease and, in combination with fine needle aspiration, a specificity of 100 % for metastasis. The majority of patients diagnosed during their childbearing years present with palpable in-breast disease and many have concomitant gross axillary involvement; therefore, sonographic evaluation and needle aspiration of the axilla preoperatively should be strongly considered, particularly in the gravid population. For the clinically node-negative pregnant patient, the practice of sentinel node biopsy is one that has been evaluated using non-pregnant human models in a variety of settings, primarily with Tc-99 lymphoscintigraphy, all of which have demonstrated clinically insignificant levels of potential radiation dose to the gravid uterus. One study has also examined the utility of methylene blue dye lymphoscintigraphy, although this has generally been avoided due to concerns of allergy and transplacental exchange. Although small datasets, these studies represent the only feasible prospective data due to the ethical and practical constraints of conducting research in a pregnant population. In this issue of Annals of Surgical Oncology, Gropper et al. reviewed the 16 years single-institution experience of sentinel node biopsy in pregnancy. Their results mirror other small single-institution series supporting the safety and efficacy of sentinel node biopsy in pregnancy. However, this practice is not isolated; the National Comprehensive Cancer Network (NCCN) Breast Cancer guidelines suggest the discussion of sentinel node biopsy with Tc-99 in the setting of pregnancy and clinically nodenegative breast cancer. Society of Surgical Oncology 2014Breast cancer in the premenopausal population is uncommon, and breast cancer diagnosed in pregnancy is a frankly rare event, occurring in approximately 1/3,000 breast cancer cases annually. Considering the recent national and international trend of deferred childbearing, the incidence of breast cancer in pregnancy is likely to remain the same or increase in the coming years. Happily, breast cancer patients have been the beneficiaries of cutting edge cancer therapy in all modalities. These advances have not only significantly improved quality of life, they have also had a marked effect on the longevity of women diagnosed with breast cancer, even those presenting with late-stage disease. Thus, it is our responsibility as surgeons and oncologists to offer this special population the best that modern medicine has on hand. However, we frequently fall short of this goal when treating the pregnant breast cancer patient due to a lack of knowledge, the paucity of data, as well as fear for the potential current and future effects of therapy on the fetus. Although complicated by the timing of pregnancy, the data suggest that many of the surgical options recommended to non-pregnant patients should be considered for the gravid breast cancer patient, and termination of the pregnancy is by no means therapeutic. Given that the tumor biology seen in pregnant patients is similar to the nonpregnant premenopausal population, and that survival is dictated by tumor biology rather than the presence of a fetus, advocacy of the ‘therapeutic abortion’ is not only outdated but it borders on unethical. Unfortunately, the myth of the ‘therapeutic abortion’ continues to persist in the medical community, even to this day. For the newly-diagnosed pregnant patient, advances in breast imaging, particularly ultrasound, should not be forgotten. In particular, ultrasound of the axilla had demonstrated high sensitivity for axillary disease and, in combination with fine needle aspiration, a specificity of 100 % for metastasis. The majority of patients diagnosed during their childbearing years present with palpable in-breast disease and many have concomitant gross axillary involvement; therefore, sonographic evaluation and needle aspiration of the axilla preoperatively should be strongly considered, particularly in the gravid population. For the clinically node-negative pregnant patient, the practice of sentinel node biopsy is one that has been evaluated using non-pregnant human models in a variety of settings, primarily with Tc-99 lymphoscintigraphy, all of which have demonstrated clinically insignificant levels of potential radiation dose to the gravid uterus. One study has also examined the utility of methylene blue dye lymphoscintigraphy, although this has generally been avoided due to concerns of allergy and transplacental exchange. Although small datasets, these studies represent the only feasible prospective data due to the ethical and practical constraints of conducting research in a pregnant population. In this issue of Annals of Surgical Oncology, Gropper et al. reviewed the 16 years single-institution experience of sentinel node biopsy in pregnancy. Their results mirror other small single-institution series supporting the safety and efficacy of sentinel node biopsy in pregnancy. However, this practice is not isolated; the National Comprehensive Cancer Network (NCCN) Breast Cancer guidelines suggest the discussion of sentinel node biopsy with Tc-99 in the setting of pregnancy and clinically nodenegative breast cancer. Society of Surgical Oncology 2014