Early-Stage (I–II) Breast Cancer

Updated by Emma B. Holliday

BACKGROUND

What histologic subtypes of invasive ductal carcinoma (IDC) are associated with favorable outcomes?

Tubular, medullary, mucinous (colloid), and papillary

What is a phyllodes tumor of the breast?

Previously known as cystosarcoma phyllodes, phyllodes tumor ranges from benign to malignant and is a rare tumor with leaflike, lobulated appearance on microscopic section. Surgery is the primary treatment: wide local excision (with at least 1-cm margins) or total mastectomy; surgical axillary evaluation is not indicated in clinically node-negative pts. Per NCCN 2014, there is no standard role for RT after either mastectomy or wide local excision with adequate margin. The role of RT after breast conservation surgery (BCS) for large and/or malignant phyllodes tumors is still undefined, however.

What is Paget Dz of the breast? What is the clinical presentation?

Paget Dz of the breast is caused by malignant epithelial cells (Paget cells) infiltrating the epidermis of the nipple-areolar complex. The clinical presentation is crusting, scaling, itching, and redness on the skin of the nipple that can progress to ulceration and bleeding. 80%–90% of Paget Dz is associated with underlying ductal carcinoma in situ (DCIS) or invasive breast cancer.

What % of invasive cancers are lobular carcinomas?

10%–15% of invasive cancers are lobular carcinomas.

According to the NSABP B04 trial, what % of women with a clinically – axilla were found to have axillary mets at LND?

Per NSABP B04, 40% of these women had axillary mets at LND.

Of the women who had a clinically – axilla and did not have a nodal dissection, what % eventually developed a clinically + axilla?

20% of these women developed a clinically + axilla.

WORKUP/STAGING

What is the workup for invasive breast cancer?

Per NCCN 2014, H&P (including family Hx of breast or ovarian cancer, personal Hx of atypical ductal or lobular hyperplasia), CBC, LFTs, diagnostic bilat mammogram, estrogen receptor (ER)/progesterone receptor (PR)/HER2 status, and β-HCG (if premenopausal), and offer genetic counseling if at risk for hereditary breast cancer. Other imaging only for suspicious Hx, physical, or lab findings.

What is the role of MRI for pts with known invasive breast cancer?

Per NCCN 2014, MRI can be used to define the extent of Dx/multifocal Dz in the ipsi breast or for contralat Dz (cat. 2B). There is no evidence that MRI improves LR or OS.

How should the axilla be staged?

If palpable or radiologically visible LN, FNA/core Bx to confirm → full axillary lymph node dissection (ALND) (levels I and II) at the time of surgery. If no palpable or radiologically visible LN, sentinel lymph node dissection (SLND) is preferred over ALND in early-stage Dz.

Which major trials showed SLND Bx as an alternative to ALND for sentinel node–negative pts?

The NSABP B-32 trial randomized 5,611 pts undergoing mastectomy or lumpectomy to SLN Bx + immediate completion axillary LND vs. SLN Bx alone. The OS, DFS, and regional control were statistically similar between groups. The 10-yr OS was 87.8% vs. 88.9%, DFS 76.9% for both, and LR rate 4.3% vs. 4.0%, for SLND alone vs. SLND + ALND, respectively. (KragDN et al., Lancet Oncol 2010; 10-yr update ASCO 2013) The ALMANAC trial (Mansel RE et al., JNCI 2006) and Milan trial (Veronesi U et al., NEJM 2013; Lancet Oncol 2006; 10-yr update Ann Surg 2010) also showed comparable outcomes. Both NSABP B32 and ALMANAC showed a decreased risk of lymphedema and arm numbness with SLN Bx.

What should be done if the SLND is positive?

If T1 or T2 tumor, 1 or 2 + SLN, whole breast irradiation (WBI) is planned after lumpectomy and no neoadj systemic therapy was given, no further surgery may be considered (NCCN 2014). American College of Surgeons Oncology Group (ACOSOG) Z0011 randomized ALND (n = 445) vs. no dissection (n = 445) for +SLND Tx with WBI (tangents) but no dedicated axillary RT. Study closed (891 of 1,900) early b/c of low accrual and no expected change in results with full accrual. SLND alone did not result in inferior 5-yr OS (91.8% vs. 92.5%), DFS (83.9% vs. 82.2%), or LRR-free survival (96.7% vs. 95.7%). (Giuliano AE et al., JAMA 2011)

List the subsets of T1 breast cancers per the 7^th edition of AJCC.

Per AJCC 7^th edition (2011):

T1mic: ≤0.1 cm

T1a: >0.1 but ≤0.5 cm

T1b: >0.5 cm but ≤1 cm

T1c: >1 cm but ≤2 cm

Define T2 and T3.

T2: >2 cm but ≤5 cm

T3: >5 cm

What is the pathologic staging for N0?

pN0(i–): no LN met histologically, negative immunohistochemistry (IHC)

pN0(i+): malignant cells/cell clusters ≤0.2 mm or ≤200 cells (detected by H&E or IHC, including isolated tumor cells)

What is the clinical staging for N1?

cN1: mets to any number of movable ipsi levels I–II axillary nodes

What is the pathologic staging for N1?

pN1mic: micrometastases (>0.2 mm or 200 cells but ≤2.0 mm)

pN1a: 1–3 axillary nodes, at least 1 with >2.0 mm mets

pN1b: micro- or macrometastases in internal mammary nodes, detected only by SLN Bx

pN1c: micro- or macrometastases in internal mammary nodes, detected only by SLN Bx AND in 1–3 axillary nodes

What is the TNM staging for stage I breast cancers?

IA: T1 N0

IB: T1 N1mic

What is the TNM staging for stage II breast cancers?

IIA: T1 N1, T2 N0

IIB: T2 N1, T3 N0

What % of breast cancer pts are diagnosed with stages 0–II Dz?

~80% of breast cancer pts are diagnosed with stages 0–II Dz according to the most recent SEER statistics

How should Paget Dz associated with an underlying breast cancer be staged?

Per the AJCC 7^th edition (2011), Paget Dz associated with underlying breast cancer should be staged according to the T stage of the underlying cancer (Tis, T1, etc.).

TREATMENT/PROGNOSIS

What are the management options for early-stage breast cancers?

Early-stage breast cancer management options:

1. Total mastectomy +/– systemic therapy +/– RT

2. Breast conservation therapy (BCT = breast conservation surgery [BCS] + RT) +/– systemic therapy

Options for delivery of RT as a component of BCT include WBI +/– boost, hypofractionated WBI +/– boost, or accelerated partial breast irradiation via external beam, interstitial, or intracavitary brachytherapy.

When should adj chemo be utilized in the management of early-stage node-negative breast cancers?

1. TN or HER2/neu (H2N +): tumor >1 cm (consider for tumor 0.6–1 cm)

2. ER+ AND H2N- AND tumor >0.5 cm: consider using 21 gene assay (Oncotype DX to determine role of adj chemo).

What does the Oncotype DX score tell you?

Risk of distant recurrence within 10 yrs of Dx with 5 yrs endocrine therapy alone in ER+, N0 pts who undergo upfront surgery.

Low recurrence score (<18) → adj endocrine Tx

Intermediate recurrence score (18–30) → adj endocrine +/– chemo

High recurrence score (≥31) → adj endocrine + chemo

When should adj endocrine therapy be used in early-stage breast cancer?

ER+ AND tumor >0.5 cm (consider for tumors £0.5 cm)

What are some general principles of administering adj endocrine therapy?

General principles for administration of adj endocrine therapy:

1. If the pt is premenopausal, tamoxifen (20 mg/day) is given for 5 yrs. Consider an additional 5 yrs of tamoxifen (if pt remains premenopausal) or an aromatase inhibitor (AI).

2. If the pt is postmenopausal, AI × 5 yrs is the most common approach. For women who cannot or will not take an AI, tamoxifen × 5 yrs and consider an additional 5 yrs of tamoxifen

What is the major contraindication to the use of AIs?

Premenopausal status or unknown menopausal status. AIs are not effective in women with estrogen-producing ovaries.

What are the major side effects of tamoxifen and AIs?

Tamoxifen: blood clots, strokes, uterine cancer, and cataracts. Gyn exam every 12 mos should be performed in women with a uterus.

Aromatase inhibitors: bone loss and osteoporosis, as well as joint pain and stiffness. Bone mineral density should be assessed at baseline and monitored periodically.

What are the major chemo agents used in breast cancer?

A: doxorubicin

E: epirubicin

C: cyclophosphamide or carboplatin

T: paclitaxel or docetaxel

F: 5-FU

H: trastuzumab

What are the major chemo combinations used in breast cancer?

AC: doxorubicin + cyclophosphamide

EC: epirubicin + cyclophosphamide

FAC/FEC: 5-FU, doxorubicin/epirubicin, cyclophosphamide

AC/EC/FAC/FEC + T: the T is paclitaxel

TC: docetaxel + cyclophosphamide

TCH: docetaxel + carboplatin + trastuzumab

What chemo regimens are recommended for HER2– tumors?

The preferred chemo regimens are:

1. Dose-dense AC (q2wk × 4 instead of q3wk × 4–6) followed by paclitaxel q2wk × 4

2. Dose-dense AC followed by paclitaxel q1wk × 12

3. TC q3wk × 4–6

What chemo regimens are recommended for HER2+ tumors?

The preferred chemo regimens are:

1. AC followed by T plus concurrent trastuzumab (various schedules), followed by single-agent trastuzumab q3wk for a total of 1 yr

2. TCH q3wk × 6, followed by single-agent trastuzumab q3wk for a total of 1 yr

What data support the equivalence of BCT (lumpectomy + radiotherapy) to mastectomy with regard to survival?

Several large randomized trials (NSABP B06, Milan III, Ontario, Royal Marsden, EORTC 10801) support this, but B06 has the longest (20-yr) follow-up data. Recent Oxford meta-analysis summarizes the data and survival outcomes:

NSABP B06 (Fisher B et al., NEJM 2002): 1,851 stages I–II pts randomized to (a) total mastectomy, (b) lumpectomy alone, or (c) lumpectomy + RT (50 Gy). 20-yr follow-up results showed that there was no difference in DFS, OS, or DM.

EBCTCG Oxford meta-analysis (EBCTCG Collaborators, Lancet 2011): 10,801 women enrolled in 17 trials for BCS +/– RT. The 10-yr 1^st recurrence risk reduction was 15.7% (19.3% in RT vs. 35% in BCS alone). The 15-yr breast cancer mortality was reduced by 3.8% (21.4% vs. 25.4%) with RT. Pts with pN0 Dz had 15.4% and 3.3% absolute reduction in recurrence and breast cancer mortality. Pts with pN+ Dz had 21.2% and 8.5% absolute risk reduction in recurrence and breast cancer mortality, respectively. For all risk groups, RT halves the risk of recurrence and decreases breast cancer mortality by one-sixth. For every 4 women prevented to have LR, 1 woman is saved (4:1 ratio).

What % of pts are eligible for BCT for early-stage breast cancers?

In early-stage breast cancers, 75%–80% of pts are eligible for BCT. (Morrow M et al., Cancer 2006)

What are the contraindications for BCT for pts with early-stage breast cancer?

Contraindications for BCT in early-stage breast cancer:

1. Prior RT to the chest

2. Extent of Dz that excision could not achieve –margins with an acceptable cosmetic result (note that multicentricity and multifocality are not necessarily contraindications to BCT).

3. Diffuse microcalcifications

4. 1^st or 2^nd trimester of pregnancy

5. Persistently +margin

6. Collagen vascular Dz (esp scleroderma)

(NCCN 2014)

Is there a contraindication for BCT in pts with a positive family Hx of breast cancer?

No. There is no evidence that demonstrates increased ipsi or contralat breast cancers in pts with a positive family Hx after BCT. (Vlastos G et al., Ann Surg Oncol 2007)

Are BRCA mutations a contraindication for BCT?

No. Multiple case-control studies have not established a higher ipsi breast tumor recurrence (IBTR) rate in BRCA1/BRCA2 mutation carriers compared to wild-type individuals, particularly if oophorectomy is performed in BRCA carriers. However, contralat breast cancer development is a major risk for BRCA carriers. Contralat breast cancer risk can be reduced with tamoxifen, oophorectomy, or both, but is most effectively reduced with prophylactic total mastectomy. BRCA+ breast cancer pts who elect contralat prophylactic total mastectomy will frequently also choose an ipsi total mastectomy for Tx of their known breast cancer.

What are the dose fractionation schedules for WBI?

Standard fractionation schedules:

1. 50 Gy in 2 Gy fx

2. 45–50.4 Gy in 1.8 Gy fx

Hypofractionated schedules:

1. 42.56 Gy in 2.67 Gy fx

2. 40.05 Gy in 2.67 Gy fx

What data support the use of hypofractionated WBI?

4 randomized trials with ≥10-yr follow-up suggest the same outcomes using a hypofractionated approach, with potentially better side effect profile. (Canadian, START pilot, START A/B trials).

Canadian regimen (Whelan TJ et al., JNCI 2002; Whelan TJ et al., NEJM 2010): RCT using 42.5 Gy in 16 fx (2.65 Gy/fx) vs. 50 Gy in 25 fx (2 Gy/fx) with no boost; 1,234 T1-2N0 pts, all with –surgical margins (SMs). Women with >25-cm breast width were excluded (to reduce heterogeneity of dose to the breast). 10-yr follow-up: no difference in LR, DFS, or cosmesis. Good to excellent cosmesis was equivalent (71.3% standard vs. 69.8% hypofractionated).

British regimen (START A/B trials, Lancet 2008): 2,215 women with pT1-3N0-1 s/p surgery randomized to 50 Gy in 25 fx vs. 40 Gy in 15 fx (2.67 Gy/fx). Boost and adj systemic Tx were optional. After 6-yr follow-up, there was no difference in IBTR (3% vs. 2%). 10-yr results published in abstract form at the San Antonio Breast Cancer Symposium in 2012 (Cancer Res, 72(24), 2012, suppl. 3): no difference in locoregional relapse between the 50-Gy and 40-Gy arms. Physician assessed markers of cosmetic outcome better with hypofractionation. Outcomes did not vary by age, BCS vs. mastectomy, nodal status, tumor grade, or the receipt of boost or adj chemo.

According to ASTRO guidelines, who can be offered hypofractionated WBI?

ASTRO guidelines (Smith BD et al., IJROBP 2011) state task force consensus for pts meeting all these criteria:

1. ≥50 yo

2. pT1-2N0, treated with BCS

3. No systemic chemo

4. Good homogeneity: dose along central axis +/– 7% of Rx dose.

What data support the use of a tumor bed boost?

2 studies have demonstrated an improved LC rate with a 10–16 Gy boost after initial whole breast dose to 45–50 Gy:

EORTC boost trial (Bartelink K et al., JCO 2007): 5,318 women with BCT, 10-yr update: 50 Gy vs. 50 Gy + 16 Gy boost (SM–) or + 26 Gy boost (SM+). 10-yr LF: 6.2% + boost vs. 10.2% – boost. Absolute benefit was greatest in women <50 b/c they have a higher risk of LR (24% – boost vs. 13.5% + boost for women <40 yo), but proportional benefits were seen across all age groups.

Lyon boost trial (Romestaing P et al., JCO 1997): 1,024 pts, 50 Gy vs. 50 Gy + 10 Gy boost. At 3-yr follow-up, LF was reduced in the boost arm (3.6% vs. 4.5%).

In general, a boost of 10–16 Gy should be considered for all pts, and should always be administered for pts at higher risk for LR (age <50 yrs, +LVI, or close SMs). This can be administered with brachytherapy, electrons, or photons.

Is there a need for a higher tumor boost dose in pts with incomplete tumor excision after BCS?

No. In the EORTC boost trial, 251 pts with microscopically incomplete tumor excision were randomized to low (10 Gy) vs. high (26 Gy) boost. With median follow-up of 11.3 yrs, there was no difference in LC or survival. There was significantly more fibrosis in the high-dose arm. (Poortmans PM et al., Radiother Oncol 2009)

What is the next step in the management for a pt who undergoes a lumpectomy with a focal +margin?

This is controversial. Most would advocate taking the pt back to surgery for re-excision, which may diminish the 10-yr risk of LR to baseline levels (initial SM–: 7%, SM+: 12%; SM close: 14%; re-excision SM–: 7%, re-excision persistent SM+: 13%, re-excision persistent SM close: 21%). (Freedman G et al., IJROBP 1999)

Is there a subset of women whose LR risk may not be substantially influenced by margin positivity after BCS?

Possibly. There are data to suggest that the effect of margin positivity on LR may be dependent on age <40 yrs. In an analysis of 1,752 pts, 193 were SM+. Overall 10-yr LR rate was 6.9% (SM–) vs. 12.2% (SM+). 5-yr LR rate for pts ≤40 yo was 8.4% (SM–) and 37% (SM+) (p = 0.005); for pts >40 yo, the LR rate was 2.6% (SM–) and 2.2% (SM+). (Jobsen JJ et al., IJROBP 2003)

Should women with T1-2N0 invasive breast cancer treated with mastectomy to a +margin be treated with adj RT to the chest wall as well?

In a British Columbia retrospective study (Truong PT et al., IJROBP 2004), of 2,570 women with early-stage breast cancer treated with mastectomy, 94 pts had a +margin. About half (41 pts) were treated with postmastectomy RT (PMRT). B/c of the small numbers, there was a trend to improvement with PMRT in pts £50 yrs, T2 tumor, grade III, and LVI. In pts without these features, there was no LR without PMRT.

What is EIC?

EIC (extensive intraductal component) is defined as DCIS both admixed and adjacent to invasive Dz, and comprising >25% of the total tumor mass. DCIS with focal microinvasive Dz also fits this category.

Does EIC have prognostic significance in the LR risk of pts treated with BCT?

Yes, but it is largely dependent on SM status. From studies mainly out of JCRT, EIC is only prognostic for LF if the margin status is considered. If there is a close or +margin, EIC is associated with a higher risk of recurrence. (Gage I et al., Cancer 1996)

What data suggest that results of BCT can be further improved with the use of tamoxifen?

NSABP B21 (Fisher B et al., JCO 2002): 1,009 pts with ≤1-cm tumors s/p lumpectomy randomized to 3 arms: (a) tamoxifen alone (10 mg bid × 5 yrs), (b) RT alone (50 Gy), and (c) RT + tamoxifen. After 8-yr follow-up, the IBTR was 16.5% with tamoxifen alone vs. 9.3% with RT alone vs. 2.8% with RT + tamoxifen. There was no difference in OS. No benefit was seen in ER– tumors. Contralat breast tumor recurrence was 0.9%, 4.2%, and 3.0% in the 3 arms, respectively.

Are there pt subgroups with a low risk of LR who can be treated with BCS and systemic therapy alone without RT?

Yes. Recent trials suggest that pts with advanced age (≥60–70 yrs) and ER+ T1N0 tumors have an acceptably low rate of LR with surgery and endocrine Tx, although LR risk is further reduced by RT. The data suggest that the risk is very low only for pts >70 yo and possibly in those with very small tumors (<1 cm), so a discussion can be made about withholding RT if the pt is being treated with tamoxifen. The 2 most important trials are the Toronto and CALGB 9343/Intergroup trials:

Princess Margaret Hospital/Canadian trial (Fyles AW et al., NEJM 2004): 769 women ≥50 yo (median age 68 yrs) with T1 or T2 (≤5 cm) –nodes (in women age ≥65 yrs, either clinical or pathologic evaluation was sufficient and SLN Bx was not routinely done) underwent lumpectomy to –margins and were randomized to (a) tamoxifen alone (20 mg/day × 5 yrs) vs. (b) tamoxifen + RT (40 Gy in 16 fx with a boost of 12.5 Gy in 5 fx). After 8-yrs follow-up, RT reduced LR from 17.6% to 3.5%. But for tumors ≤1 cm, the risk of relapse was 2.6% vs. 0% for the RT group (p = 0.02). In those ≥60 yo with ≤1-cm tumor, the risk was no different between the 2 arms (1.2% vs. 0%), but this was unplanned analysis with a short follow-up.

CALGB 9343/Intergroup trial (Hughes KS et al., NEJM 2004; updated JCO 2013): 636 women ≥70 yo with T1, clinically N0, ER+ tumors were randomized to tamoxifen vs. tamoxifen + RT after lumpectomy with –margins. Axillary dissection was allowed but not encouraged. RT was 45 Gy to the whole breast with a boost of 14 Gy. At a median of 12.6 yrs follow-up, the 10-yr LF rate in the tamoxifen alone arm was 10% vs. 2% in tamoxifen + RT. There was no difference in time to mastectomy, DM, breast cancer survival, or OS.

Can RT be used in the Tx of axillary nodes in place of surgery if axillary nodal dissection is not performed?

Possibly. Previous era trials in clinically node– pts (esp NSABP B04 and Institut Curie) have demonstrated equivalent LC, DM, and OS with nodal RT vs. axillary dissection. In the modern era, the AMAROS (After Mapping of the Axilla: Radiation or Surgery) trial randomized SLN+ pts to completion ALND or nodal RT; 5-yr results showed no significant difference in LRR, DM, or OS and overall better arm function in the RT arm (data not yet published).

Are there data supporting WBI + regional nodal irradiation (RNI) for early-stage breast cancer?

Yes, although the data are not yet published in manuscript form. NCIC-CTG MA.20 is a randomized trial that enrolled 1,832 N+, T3N0, or high risk T2N0 pts treated with BCS + axillary surgical evaluation, adj chemo in >90%, +/– endocrine Tx. Randomized to WBI (50 Gy/25 fx +/– boost) or WBI + RNI (45 Gy/25 fx) to axillary apex, internal mammary chain and supraclavicular. 85% had 1–3 +LN. WBI + RNI had improved 5-year locoregional DFS (96.8% vs. 94.5%), distant DFS (92.4% vs. 87%), and a trend toward OS (92.3% vs. 90.7%). (Whelan T, JCO 29: 2011, suppl; abstr LBA1003)

How should chemo be sequenced with radiotherapy after BCS?

JCRT sequencing trial (“Upfront-Outback” trial) (Bellon J et al., JCO 2005): per the initial report (Recht A et al., NEJM 1996), the 5-yr crude rate of distant recurrence was better in the chemo 1^st arm (20% vs. 32%). However, in the 11-yr follow-up update, there was no difference in DFS, LR, DM, or OS. For those with a –margin, the crude LR rate was 6% in the chemo 1^st arm vs. 13% in the RT 1^st arm. However, the study was not powered to show any differences. Thus, either sequence is acceptable. However, convention is to give chemo 1^st.

What U.S. trial investigated the role of accelerated partial breast irradiation (APBI)?

NSABP B39/RTOG 0413, which randomized women with stage 0, 1, or 2 breast cancer with tumors ≤3 cm and ≤3 +LN to whole breast RT vs. APBI by any of 3 methods (interstitial, intracavitary, or EBRT).

What is the dose and duration of Tx for APBI?

34 Gy in 3.4 Gy bid fx for interstitial and intracavitary treatments and 38.5 Gy in 3.85 Gy bid fx for EBRT. All APBI is given over 5 days. The volume treated is the surgical cavity plus a 1-cm margin for brachytherapy and a 2–2.5 cm for EBRT.

Who can be offered PBI off trial?

ASTRO has published guidelines on who may be considered for PBI off trial. (Smith BD et al., IJROBP 2009) “Suitable” pts are >60 yo, ER+, IDC ≤2 cm (no DCIS or invasive lobular carcinoma), N0, unicentric, ≥2-mm margin, no LVSI, no EIC, and BRCA1/BRCA2–. The ABS updated guidelines (Shah C et al., Brachytherapy 2013) state “acceptable” pts are ≥50 yo, £3-cm tumor, invasive subtypes and DCIS, either ER+ or ER-, no LVSI, N0.

Is there good evidence to support the use of IMRT for WBI for early-stage breast cancer?

Emerging data seem to indicate that homogeneous dose distribution of IMRT benefits pts in terms of acute effects and late-term cosmesis.

Canadian study (Pignol JP et al., JCO 2008) demonstrated in 358 pts that IMRT reduced the occurrence of moist desquamation compared with standard wedge technique (31.2% vs. 47.8%, p = 0.002). MVA shows breast IMRT and smaller breast size were associated with decreased risk of moist desquamation.

British study (Mukesh MB et al., JCO 2013) showed in 1,145 pts with 5-yr follow-up that overall cosmesis was improved with IMRT compared with standard techniques (OR 0.68, p = 0.027) as well as skin telangiectasia (OR 0.58, p = 0.021). This benefit was maintained on multivariable analysis.

Are there subsets of women who undergo mastectomy for early-stage breast cancers (T1-2N0) who may benefit from PMRT?

Only in limited circumstances. NCCN 2014 guidelines recommend consideration of RT for node– T1-T2 close or positive margins. Retrospective data suggest that some margin– high-risk pts (LVSI, high grade, T2 tumors, young age) have an excess risk of LRR after mastectomy. However, PMRT in node– pts does not improve survival per EBCTCG 2005 meta-analysis data, and at this time PMRT for high risk T1-2N0 in the absence of close or +margins is counter to standard of care.

How should a Dx of breast cancer be managed in a pregnant woman?

Management depends on the stage of pregnancy. Timing of surgery depends on need for chemo and relative risks to fetus and mother. Chemo can be used to delay surgery until after delivery. Nontaxane chemo (most commonly, FAC) can be used in the 2^nd and 3^rd trimesters of pregnancy; chemo should be discontinued 3 wks before expected delivery to reduce infection and bleeding risks. RT and endocrine therapy must be deferred until postpartum.