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Keywords:

  • Trastuzumab;
  • HER2;
  • breast cancer;
  • node-negative

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

BACKGROUND:

Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node-negative HER2-positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single-institution, sequential cohort study of women with small, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted.

METHODS:

Women with ≤2 cm, node-negative, HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization ≥2) breast cancer were identified through an institutional database. A “no-trastuzumab” cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004 and a “trastuzumab” cohort of 155 trastuzumab-treated women diagnosed between May 16, 2005 and December 31, 2008 were described. Survival and recurrence outcomes were estimated by Kaplan-Meier methods.

RESULTS:

The cohorts were similar in age, median tumor size, histology, hormone receptor status, hormone therapy, and locoregional therapy. Chemotherapy was administered in 66% and 100% of the “no trastuzumab” and “trastuzumab” cohorts, respectively. The median recurrence-free and survival follow-up was: 6.5 years (0.7-8.5) and 6.8 years (0.7-8.5), respectively, for the “no trastuzumab” cohort and 3.0 years (0.5-5.2) and 3.0 years (0.6-5.2), respectively, for the “trastuzumab” cohort. The 3-year locoregional invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival were 92% versus 98% (P = .0137), 95% versus 100% (P = .0072), 82% versus 97% (P < .0001), and 97% versus 99% (P = .18) for the “no trastuzumab” and “trastuzumab” cohorts, respectively.

CONCLUSIONS:

Women with small, node-negative, HER2+ primary breast cancers likely derive significant benefit from adjuvant trastuzumab with chemotherapy. Cancer 2011;. © 2011 American Cancer Society.

Amplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) confers a poor prognosis, even for women with small, node-negative early-stage breast cancer.1-5 However, the widespread administration of adjuvant chemotherapy and HER2-targeted therapy with trastuzumab has largely ameliorated this adverse prognosis for women with node-positive and “high-risk” node-negative, HER2-positive (HER2+) breast cancer.6-10 Since the first trials were reported on May 15, 2005,7, 8 several additional randomized studies have confirmed, with high reproducibility, the recurrence and survival benefits with adjuvant chemotherapy-trastuzumab in selected populations.11, 12 However, because women with small, node-negative, HER2+ breast cancers were largely excluded from these studies, it is not definitively known whether adjuvant trastuzumab-based therapy confers benefits in this lower-risk population. Furthermore, because of the modest event rate in this lower-risk population, a prospective randomized study may not be feasible. Despite the absence of existing (and perhaps forthcoming) data, clinicians are routinely faced with the challenge of making treatment recommendations for women who do not meet historical study criteria.

To address the potential role of trastuzumab in low-risk patients, who would largely have been excluded from the key randomized adjuvant trials, we conducted a single-institution, retrospective study of women with ≤2 cm, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab therapy. The decision to use trastuzumab was time dependent (pre- vs post-reporting of the adjuvant trials), thereby possibly minimizing uncontrolled confounding factors.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

All women with pathologically confirmed, ≤2 cm, node-negative, HER2+ invasive breast cancer diagnosed between January 1, 2002 and December 31, 2008 and evaluated at Memorial Sloan-Kettering Cancer Center (MSKCC) for early-stage breast cancer management and completing definitive locoregional therapy were identified through an institutional database. Patients with isolated tumor cells ≤0.2 mm in lymph nodes [pN0(i+)]13 were included. HER2+ was defined as 3+ by immunohistochemistry (IHC) and/or ≥2 (HER2 to chromosome 17 centromere signals) by fluorescence in situ hybridization (FISH). Women with bilateral invasive breast cancer; any concurrent, invasive secondary cancer; inadequate locoregional and/or systemic therapy documentation; or treatment with other adjuvant HER2-targeted agents including lapatinib were excluded. Women with a prior history of invasive breast cancer, anthracycline and/or taxane therapy, any metastatic cancer, or mantle irradiation were also excluded.

To eliminate confounding by variable clinical practice patterns around May 15, 2005 when the results from the prospective randomized trials were reported, we excluded women diagnosed between May 15, 2004 and May 15, 2005, thereby eliminating patients diagnosed the year before the announcement who might have been offered delayed trastuzumab.

Two cohorts of eligible women were ultimately identified: a “no trastuzumab” cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004, and a “trastuzumab” cohort of 155 trastuzumab and chemotherapy–treated women diagnosed between May 16, 2005 and December 31, 2008 (with trastuzumab initiated concurrently or within 8 weeks of chemotherapy completion). Because evidence from a prospectively conducted, randomized study indicates that a brief course12 may confer comparable benefits to a 1-year course of trastuzumab,9-11 the duration of trastuzumab administration did not impact “trastuzumab” cohort eligibility.

Patient and tumor characteristics were recorded for all eligible patients. Overall survival was defined as the time from diagnosis to date of death or the last direct patient communication of any kind. For the 3 breast cancer–specific recurrence end points (locoregional, contralateral, and distant), the final follow-up date for each patient was defined as the date of locoregional invasive recurrence, contralateral invasive recurrence, distant recurrence, or last breast cancer status evaluation by any MSKCC physician, MSKCC survivorship nurse practitioner, non-MSKCC oncologist, and/or non-MSKCC primary care physician.

Locoregional invasive recurrence-free, contralateral new primary/invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival at 1, 2, and 3 years were estimated with 95% confidence intervals for each cohort by the Kaplan-Meier method. Outcome estimates were compared using the log-rank test. Invasive disease-free survival was defined by the occurrence of any of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, contralateral invasive breast cancer, or second primary nonbreast invasive cancers.17

To account for the differences in follow-up for the 2 cohorts, 3 years (the median recurrence-free and overall survival follow-up for women in the “trastuzumab” cohort) was identified as the optimal time point for cohort comparison (a time point that is further supported by the observation that HER2+ breast cancers tend to recur early overall3, 4). Consequently, the 3-year locoregional invasive recurrence-free, contralateral invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival estimates are highlighted.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

Overall

Baseline characteristics for the 106 women in the “no trastuzumab” and the 155 women in the “trastuzumab” cohorts are shown in Table 1. The median age was 51 years (range, 23-84) for the “no trastuzumab” cohort and 52 years (28-81) for the “trastuzumab” cohort. The median tumor size was similar for the 2 cohorts, although the proportion of 1.6-2.0 cm tumors was higher in the “trastuzumab” cohort and the proportion of ≤0.5 cm tumors was higher in the “no trastuzumab” cohort. More women in the “trastuzumab” cohort had lymphovascular invasion (21% vs 11%). All women in the “trastuzumab” cohort received adjuvant chemotherapy versus 66% of the “no trastuzumab” cohort. Otherwise, no meaningful differences were observed between the 2 cohorts. For the 155 women in the “trastuzumab” cohort, the mean adjuvant trastuzumab delivery period was 52 weeks (range, 1-68). Two patients tolerated chemotherapy without notable toxicity but refused further therapy after only 1 week of trastuzumab: 1 woman received 8 mg/kg with the first planned cycle of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) but then declined any further systemic therapy; and 1 woman received 4 mg/kg with paclitaxel at 80 mg/m2 after 1 cycle of doxorubicin and cyclophosphamide (AC) but then declined any further systemic therapy because of “stress.” After 10 weeks of adjuvant trastuzumab, 1 patient was lost to follow-up for 4 months but ultimately resumed treatment and received the planned course of trastuzumab therapy over 68 weeks.

Table 1. Baseline Characteristics
 All PatientsSubset of Patients With Tumors ≤1.0 cm
 No trastuzumab (n=106)Trastuzumab (n=155)No trastuzumab (n=45)Trastuzumab (n=54)
 No. (%)No. (%)No. (%)No. (%)
  • Abbreviations: N/A, not applicable.

  • a

    Two patients declined further therapy after 1 week of trastuzumab: 1 received 8 mg/kg with paclitaxel at 175 mg/m2 and the other received 4 mg/kg with paclitaxel at 80 mg/m2. After 10 weeks of adjuvant trastuzumab, 1 patient was lost to follow-up for 4 months, but ultimately resumed treatment and received the planned course of trastuzumab therapy over 68 weeks.

Median age, y (range)51y (23-84y)52y (28-81y)51y (34-73y)54y (28-75y)
Tumor size    
Median (range)1.1 cm (≤0.1-2.0 cm)1.3 cm (0.3-2.0 cm)0.5 cm (≤0.1-1.0 cm)0.8 cm (0.3-1.0 cm)
≤0.5 cm23 (22)12 (8)23 (51)12 (22)
0.6-1.0 cm22 (21)42 (27)22 (49)42 (78)
1.1-1.5 cm37 (35)56 (36)N/A (N/A)N/A (N/A)
1.6-2.0 cm24 (23)45 (29)N/A (N/A)N/A (N/A)
Lymph node status13    
N0103 (97)151 (97)44 (98)52 (96)
N0 (i+)3 (3)4 (3)1 (2)2 (4)
Histology    
Ductal101 (95)147 (95)45 (100)52 (96)
Lobular1 (1)2 (1)0 (0)1 (2)
Mixed4 (4)6 (4)0 (0)1 (2)
Grade    
11 (1)1 (1)1 (2)1 (2)
2-396 (91)150 (97)37 (82)52 (96)
Unknown/Not recorded9 (8)4 (3)7 (16)1 (2)
Lymphovascular invasion    
Present12 (11)33 (21)4 (9)7 (13)
Absent87 (82)115 (74)38 (84)42 (78)
Suspected2 (2)3 (2)1 (2)1 (2)
Unknown/Not recorded5 (5)4 (3)2 (4)4 (7)
Hormone receptor status    
Positive64 (60)98 (63)24 (53)31 (57)
Negative40 (38)57 (37)19 (42)23 (43)
Unknown2 (2)0 (0)2 (4)0 (0)
Surgery    
Breast-conserving58 (55)84 (54)17 (38)26 (48)
Mastectomy48 (45)71 (46)28 (62)28 (52)
Received adjuvant radiotherapy60 (57)83 (54)18 (40)25 (46)
Adjuvant hormone therapy    
Yes63 (59)95 (61)24 (53)29 (54)
No40 (38)59 (38)21 (47)24 (44)
Unknown3 (3)1 (1)0 (0)1 (2)
Adjuvant chemotherapy:70 (66)155 (100)19 (42)54 (100)
Anthracycline/no taxane45 (42)15 (10)11 (24)8 (15)
Taxane/no anthracycline1 (1)40 (26)1 (2)21 (39)
Anthracycline and taxane13 (12)94 (61)4 (9)23 (43)
Other11 (10)6 (4)3 (7)2 (4)
Mean adjuvant trastuzumab delivery period (range)N/A52 weeks (1-68)aN/A52 weeks (5-56)

As of September 1, 2010, the median follow-up for women without recurrence and for survivors was 6.5 years (range, 0.7-8.5) and 6.8 years (range, 0.7-8.5), respectively, for the “no trastuzumab” cohort and 3.0 years (range, 0.5-5.2) and 3.0 years (range, 0.6-5.2), respectively, for the “trastuzumab” cohort.

Breast cancer recurrence-free and overall survival outcomes are shown in Table 2. At 3 years (the median follow-up for the nonrecurred women and survivors in the “trastuzumab” cohort), the locoregional invasive recurrence-free survival was 92% (95% CI, 86%-97%) versus 98% (95% CI, 95%-100%; P = .0137); the contralateral invasive recurrence-free survival was 98% (95% CI, 95%-100%) versus 100% (P = .0817); the distant recurrence-free survival was 95% (95% CI, 90%-99%) versus 100% (P = .0072); and the invasive disease-free survival was 82% (95% CI, 74%-90%) versus 97% (95% CI, 94%-100%; P < .0001) for the “no trastuzumab” and “trastuzumab” cohorts, respectively. Of the 8 locoregional recurrences in the “no trastuzumab” cohort, 5 were in-breast, 2 were nodal, and 1 occurred in the chest wall. Of the 2 locoregional recurrences in the “trastuzumab” cohort, 1 was in-breast and 1 was nodal.

Table 2. Follow-Up and Outcomes
 All PatientsSubset of Patients With Tumors ≤1.0 cm
 No trastuzumab (n=106)Trastuzumab (n=155)P-valueNo trastuzumab (n=45)Trastuzumab (n=54)P-value
 (95% CI)(95% CI) (95% CI)(95% CI) 
  • Abbreviations: CI, confidence interval; N/A, not applicable.

  • a

    Final follow-up date defined as the date of ipsilateral invasive recurrence, contralateral invasive recurrence, distant recurrence, or last breast cancer status evaluation by any Memorial Sloan-Kettering Cancer Center (MSKCC) physician, MSKCC survivorship nurse, non-MSKCC oncologist, and/or non-MSKCC primary care physician.

  • b

    To account for the differential follow-up in the two 2 cohorts, 3 years (the median recurrence-free and survival follow-up for women in the “trastuzumab” cohort) was identified as the optimal time-point for cohort comparison. Consequently, the 3-year outcomes are highlighted.

  • c

    Final follow-up date defined as the date of death or the last direct patient communication of any kind.

  • d

    No events within the preceding year.

  • e

    First and only death in the “trastuzumab” cohort occurred within the first year (cause of death unknown).

Median follow-up for non-recurred patients (range)a6.5 y (0.7-8.5)3.0 y (0.5-5.2)bN/A6.5 y (0.7-8.5)3.0 y (0.5-5.0)bN/A
Median follow-up for survivors (range)c6.8 y (0.7-8.5)3.0 y (0.6-5.2)bN/A6.7 y (0.7-8.5)3.0 y (0.6-5.1)bN/A
Locoregional invasive recurrence-free survival  .0137  .303
1-year98% (95-100)100%d 100%d100%d 
2-year93% (88-98)99% (98-100) 95% (88-100)100%d 
3-yearb92% (86-97)98% (95-100) 92% (84-100)96% (90-100) 
Number of events within 3 yearsb8 or 7.5%2 or 1.3% 3 or 6.7%1 or 1.9% 
Contralateral invasive recurrence-free survival  .0817  .2575
1-year99% (97-100)100%d 100%d100%d 
2-year98% (95-100)100%d 97% (92-100)100%d 
3-yearb98% (95-100%)d100%d 97% (92-100%)d100%d 
Number of events within 3 yearsb2 or 1.9%0 1 or 2.2%0 
Distant recurrence-free survival  .0072  .2985
1-year100%d100%d 100%d100%d 
2-year98% (95-100)100%d 100%d100%d 
3-yearb95% (90-99)100%d 97% (92-100)100%d 
Number of events within 3 yearsb5 or 4.7%0 1 or 2.2%0 
Invasive disease-free survival17  <.0001  .0198
1-year96% (93-100)99% (98-100) 98% (93-100)98% (95-100) 
2-year89% (83-95)99% (97-100) 88% (78-98)98% (95-100) 
3-yearb82% (74-90)97% (94-100) 78% (66-91)95% (87-100) 
Number of events within 3 yearsb18 or 17.0%3 or 1.9% 9 or 20%2 or 3.7% 
Overall survival  .18  .7516
1-year100%d99% (98-100%)e 100%d98% (95-100) 
2-year100%d99% (98-100%)d 100%d98% (95-100)d 
3-yearb97% (93-100)99% (98-100%)d 98% (93-100)98% (95-100)d 
Number of events within 3 yearsb3 or 2.8%1 or 0.7% 1 or 2.2%1 or 0.7% 

At 3 years, the overall survival was 97% (95% CI, 93%-100%) versus 99% (95% CI, 98%-100%; P = .18) for the “no trastuzumab” and “trastuzumab” cohorts, respectively. One death occurred in the first year of follow-up in the “trastuzumab” cohort, but no deaths were observed in the subsequent 2 years. Conversely, 3 deaths were observed within the first 3 years of follow-up in the “no trastuzumab” cohort. Unfortunately, despite efforts that included phone inquiries to the primary care physician, other involved physicians, and local hospitals, the cause of the single death that occurred in the “trastuzumab” cohort could not be ascertained.

The Kaplan-Meier curves for locoregional invasive recurrence-free, contralateral invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival are illustrated in Figure 1.

thumbnail image

Figure 1. Locoregional invasive recurrence-free (A), contralateral invasive recurrence-free (B), distant recurrence-free (C), invasive disease-free (D), and overall (E) survival for women with ≤2.0 cm, node-negative, HER2-positive breast cancer treated with or without trastuzumab.

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Subset of Women With Tumors ≤1.0 cm

Baseline characteristics for the subset of 45 women in the “no trastuzumab” and 54 women in the “trastuzumab” cohorts with tumors ≤1.0 cm are also shown in Table 1. The median age was 51 years (range, 34-73) for the “no trastuzumab” subset and 54 years (range, 28-75) for the “trastuzumab” subset. The median tumor size was slightly larger for women in the “trastuzumab” subset (0.5 cm vs 0.8 cm). More women in the “trastuzumab” subset underwent breast-conserving surgery (48% vs 38%) and received adjuvant radiotherapy (46% vs 40%). All women in the “trastuzumab” subset received adjuvant chemotherapy versus 42% of the “no trastuzumab” subset. Otherwise, no meaningful differences were observed between the two subsets.

As of September 1, 2010, the median follow-up for the subset of 45 women in the “no trastuzumab” cohort with tumors ≤1.0 cm was 6.5 years (range, 0.7-8.5) for women without a recurrence and 6.7 years (range, 0.7-8.5) for survivors. The median follow-up for the subset of 54 women in the “trastuzumab” cohort with tumors ≤1.0 cm was 3.0 years (range, 0.5-5.0) for women without a recurrence and 3.0 years (range, 0.6-5.1) for survivors.

Breast cancer recurrence-free and overall survival outcomes for the subsets are shown in Table 2. At 3 years (the median follow-up for the nonrecurred women and survivors in the ≤1.0 cm subset of the “trastuzumab” cohort), the locoregional invasive recurrence-free survival was 92% (95% CI, 84%-100%) versus 96% (95% CI, 90%-100%; P = .303); the contralateral invasive recurrence-free survival was 97% (95% CI, 92%-100%) versus 100% (P = .2575); the distant recurrence-free survival was 97% (95% CI, 92%-100%) versus 100% (P = .2985); the invasive disease-free survival was 78% (95% CI, 66% −91%) versus 95% (95% CI, 87%-100%; P = .0198); and the overall survival was 98% (95% CI, 93%-100%) versus 98% (95% CI, 95%-100%; P = .7516) for the ≤1.0 cm subsets of the “no trastuzumab” and “trastuzumab” cohorts, respectively.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

Recent studies have confirmed that HER2 status is an important prognostic feature even in women with small, node-negative breast cancer and confers higher recurrence risk than was previously estimated.3-5 Because randomized trials in this subset are unlikely to be performed, clinicians will have to rely on extrapolations from higher-risk cohorts, from underpowered subset analyses from prospectively conducted studies, and from nonrandomized data sets. For example, a recent report from a modestly powered comparison of unmatched cohorts suggested that women with small, node-negative, HER2+ breast cancer may derive benefit from adjuvant trastuzumab.14 Furthermore, a recent report from one of the prospectively conducted, randomized adjuvant trastuzumab studies indicated that the benefit of trastuzumab likely extends to the subset of women with 1.1-2.0 cm, node-negative, HER2+ breast cancer (hazard ratio, 0.53; 95% CI, 0.26-1.07).15 To address the limitations of other studies aiming to evaluate the impact of trastuzumab in low-risk populations (namely by minimizing confounding by various patient, treatment, and tumor characteristics and by including lower-risk women with subcentimeter tumors), we compared cohorts of women with small, node-negative, HER2+ breast cancers treated in the pre- and post-trastuzumab eras. Our findings were consistent with other reports and indicated that despite the conventionally favorable pathologic features, women with small, node-negative, HER2+ breast cancer appear to derive a clinically significant benefit from adjuvant trastuzumab with chemotherapy. Specifically, at 3 years, significant benefits were observed in favor of the trastuzumab-treated cohort for locoregional invasive recurrence-free survival (92% vs 98%, P = .0137), invasive disease-free survival (82% vs 97%, P < .0001), and distant recurrence-free survival (95% vs 100%, P = .0072). Furthermore, although not statistically significant, consistent benefits were observed in favor of the trastuzumab-treated cohort for contralateral invasive recurrence-free survival (98% vs 100%, P = .0817) and overall survival (97% vs 99%, P = .18). Together, the consistency of these study results with those reported in other studies support consideration of trastuzumab-chemotherapy in this population for whom, to the best of our knowledge, no randomized control trials are planned.

Because risk-benefit analyses are particularly challenging in women with subcentimeter, node-negative, HER2+ tumors, we included outcomes analyses for this subset in our study. Although underpowered to demonstrate any significant differences in individual end points, a significant difference was observed in the evaluated composite end point, invasive disease-free survival, in favor of the trastuzumab-treated subset. Specifically, at 3 years, the invasive disease-free survival was 78% versus 95% (P = .0198). Furthermore, the consistency of the other end point results with the overall study results is notable, with improved outcomes reported for the trastuzumab-treated population for every breast cancer–specific outcome including locoregional invasive recurrence-free survival, contralateral invasive recurrence-free survival, and distant recurrence-free survival. Although these results overall are underpowered to support a definitive recommendation, the consistency of the data indicates that the benefits of chemotherapy with trastuzumab even in this lower-risk subset cannot be ruled out. Unfortunately, randomized trials in this low-risk subset are unlikely.

The strengths of our study include the sample size and the balance of traditional prognostic characteristics across the 2 cohorts. Furthermore, the finding that the trastuzumab-treated cohort may have been at slightly higher risk of recurrence overall (given the higher proportion of women with lymphovascular invasion and 1.6-2.0 cm tumors) combined with the observed reduction in the event rate in this cohort strengthens our hypothesis that such patients benefit from trastuzumab-chemotherapy. In the absence of prospectively collected randomized data, these observations support clinical consideration of trastuzumab-chemotherapy even in lower-risk HER2+ populations.

The major limitation of our study is the inability to discern how much of the observed benefit can be ascribed specifically to trastuzumab versus chemotherapy administration. Unfortunately, this question can only be adequately addressed by a prospective, randomized study of, for example, trastuzumab with or without chemotherapy in this lower-risk population. Again, to the best of our knowledge, such a study is not currently planned. Our study is also retrospective, limited to a single institution, contains modest event rates, and is unable to report all details of potential interest (most notably the cause of the 1 death in the trastuzumab cohort). Although the proportion of hormone-sensitive tumors (60%) in this study was larger than that reported in a population-based study (39%),5 it was similar to the proportions reported in other single-institution studies,3, 4 suggesting either referral or hormone receptor reporting biases.

Although we lack, and are unlikely to ever obtain, randomized data addressing the role of trastuzumab in women with small, node-negative, HER2+ primary invasive breast cancers, our study suggests that these women have excellent outcomes after adjuvant chemotherapy with trastuzumab compared with a similar population of trastuzumab-untreated women. The critical issue is that approximately 10% of the approximately 200,000 new cases of invasive breast cancer anticipated in the United States in 201116 will be otherwise low risk but HER2+ is associated with an estimated 20% 5-year recurrence risk.3-5 Therefore, if our results are correct, broad use of trastuzumab with chemotherapy in this understudied population would have an important public health impact. Our data support consideration of adjuvant trastuzumab-chemotherapy for women with small, node-negative, HER2+ breast cancer.

CONFLICT OF INTEREST DISCLOSURES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

Funding sources include the Memorial Sloan-Kettering Cancer Center breast cancer fellowship support fund and the Julie Laub Fund.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES
  • 1
    Slamon D, Clark GM, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235: 177-182.
  • 2
    Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007; 25: 118-145.
  • 3
    Curigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol. 2009; 27: 5693-5699.
  • 4
    Gonzalez-Angulo AM, Litton JK, Broglio KR, et al. High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol. 2009; 27: 5700-5706.
  • 5
    Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2009; 26: 5697-5704.
  • 6
    Hudis CA. Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med. 2007; 357: 39-51.
  • 7
    Romond EH, Perez EA, Bryant J, et al. Doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab as adjuvant therapy for patients with HER-2 positive operable breast cancer—combined analysis of NSABP-B31/NCCTG-N9831. Paper presented at: Annual Meeting of American Society of Clinical Oncology; Orlando, FL, May 13-17, 2005.
  • 8
    Piccart-Gebhart M. First results of the HERA trial. Paper presented at: Annual Meeting of American Society of Clinical Oncology; Orlando, FL, May 13-17, 2005.
  • 9
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005; 353: 1673-1684.
  • 10
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005; 353: 1659-1672.
  • 11
    Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. Paper presented at: San Antonio Breast Cancer Symposium; 2005; San Antonio, TX, December 8-11, 2005.
  • 12
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006; 354: 809-820.
  • 13
    Edge SB, Byrd DR, Compton CC, et al. American Joint Committee on Cancer (AJCC) cancer staging manual. 7th ed. Chicago, IL: Springer; 2010.
  • 14
    Rodrigues MJ, Wassermann J, Albiges-Sauvin L, et al. Trastuzumab treatment in t1ab, node-negative, human epidermal growth factor receptor 2-overexpressing breast carcinomas. J Clin Oncol. 2010; 28: e541-542.
  • 15
    Untch M, Gelber RD, Jackisch C, et al. Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol. 2008; 19: 1090-1096.
  • 16
    American Cancer Society. Cancer facts and figures 2009. Available at: www.cancer.org Accessed January 23, 2011.
  • 17
    Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007; 25: 2127-2132.